System for detecting, diagnosing, and treating cardiovascular disease

ABSTRACT

A method of treating cardiovascular disease in a medical patient is provided. The method includes the steps of generating a sensor signal indicative of a fluid pressure within the left atrium of the patient&#39;s heart, and delivering an electrical stimulus to a location in the heart. The electrical stimulus is delivered based at least in part on the sensor signal. The method also includes the steps of generating a processor output indicative of a treatment to a signaling device. The processor output is based at least in part on the sensor signal. At least two treatment signals are provided to the medical patient. The treatment signals are distinguishable from one another by the patient, and are indicative of a therapeutic treatment. The treatment signals are based at least in part on the processor output.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.10/698,031, filed Oct. 9, 2003, now U.S. Pat. No. 7,483,743 which claimsthe benefit of U.S. Provisional Application No. 60/470,468, filed May13, 2003, and which is a continuation-in-part of U.S. application Ser.No. 10/127,227, Apr. 19, 2002, now U.S. Pat. No. 7,115,095, which is acontinuation of U.S. application Ser. No. 09/956,596, filed Sep. 19,2001, now abandoned, which is a continuation of U.S. application Ser.No. 09/481,084, filed Jan. 11, 2000, now U.S. Pat. No. 6,328,699, all ofwhich are incorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to systems and methods for detecting,diagnosing and treating cardiovascular disease in a medical patient.

2. Description of the Related Art

The optimum management of patients with chronic diseases requires thattherapy be adjusted in response to changes in the patient's condition.Ideally, these changes are measured by daily patient self-monitoringprior to the development of symptoms. Self-monitoring andself-administration of therapy forms a closed therapeutic loop, creatinga dynamic management system for maintaining homeostasis. Such a systemcan, in the short term, benefit day-to-day symptoms and quality-of-life,and in the long term, prevent progressive deterioration andcomplications.

In some cases, timely administration of a single dose of a therapy canprevent serious acute changes in the patient's condition. One example ofsuch a short-term disease management strategy is commonly used inpatients with asthma. The patient acutely self-administers an inhaledbronchodilator when daily readings from a hand-held spirometer offlowmeter exceed a normal range. This has been effective for preventingor aborting acute asthmatic attacks that could lead to hospitalizationor death.

In another chronic disease, diabetes mellitus, current self-managementstrategies impact both the short and long term sequelae of the illness.Diabetic patients self-monitor blood glucose levels from one to threetimes daily and correspondingly adjust their self-administeredinjectable insulin or oral hypoglycemic medications according to theirphysician's prescription (known as a “sliding scale”). More “brittle”patients, usually those with juvenile-onset diabetes, may require morefrequent monitoring (e.g., 4 to 6 times daily), and the readings may beused to adjust an external insulin pump to more precisely controlglucose homeostasis. These frequent “parameter-driven” changes indiabetes management prevent hospitalization due to symptoms caused byunder-treatment (e.g., hyperglycemia with increased hunger, thirst,urination, blurred vision), and over-treatment (e.g., hypoglycemia withsweating, palpitations, and weakness). Moreover, these aggressivemanagement strategies have been shown to prevent or delay the onset oflong-term complications, including blindness, kidney failure, andcardiovascular disease.

There are approximately 60 million people in the U.S. with risk factorsfor developing chronic cardiovascular diseases, including high bloodpressure, diabetes, coronary artery disease, valvular heart disease,congenital heart disease, cardiomyopathy, and other disorders. Another10 million patients have already suffered quantifiable structural heartdamage but are presently asymptomatic. Still yet, there are 5 millionpatients with symptoms relating to underlying heart damage defining aclinical condition known as congestive heart failure (CHF). Althoughsurvival rates have improved, the mortality associated with CHF remainsworse than many common cancers. The number of CHF patients is expectedto grow to 10 million within the coming decade as the population agesand more people with damaged hearts are surviving.

CHF is a condition in which a patient's heart works less efficientlythan it should, and a condition in which the heart fails to supply thebody sufficiently with the oxygen-rich blood it requires, either duringexercise or at rest. To compensate for this condition and to maintainblood flow (cardiac output), the body retains sodium and water such thatthere is a build-up of fluid hydrostatic pressure in the pulmonary bloodvessels that drain the lungs. As this hydrostatic pressure overwhelmsoncotic pressure and lymph flow, fluid transudates from the pulmonaryveins into the pulmonary interstitial spaces, and eventually into thealveolar air spaces. This complication of CHF is called pulmonary edema,which can cause shortness of breath, hypoxemia, acidosis, respiratoryarrest, and death. Although CHF is a chronic condition, the diseaseoften requires acute hospital care. Patients are commonly admitted foracute pulmonary congestion accompanied by serious or severe shortness ofbreath. Acute care for congestive heart failure accounts for the use ofmore hospital days than any other cardiac diagnosis, and consumes inexcess of 20 billion dollars in the United States annually.

SUMMARY OF THE INVENTION

In one embodiment of the present invention, an apparatus for treatingcardiovascular disease in a medical patient is provided. The apparatusincludes a sensor, an implantable cardiac rhythm management apparatus,an implantable lead, a signal processor, and a signaling device. Thesensor is operable to generate a sensor signal indicative of a fluidpressure within a left atrium of a heart. The cardiac rhythm managementapparatus includes a housing and an electrode, where the electrode isoperable to deliver an electrical stimulus to a location in the heart,and where the electrical stimulus is based at least in part on thesensor signal. The implantable lead is coupled to the implantablehousing and to the electrode. The signal processor is operable togenerate a processor output indicative of a treatment, where theprocessor output is based at least in part on the sensor signal. Thesignaling device is operable to generate at least two treatment signalsdistinguishable from one another by the patient, where each signal isindicative of a therapeutic treatment and where the treatment signalsare based at least in part on the processor output.

In another embodiment of the invention, an apparatus for treatingcardiovascular disease in a medical patient that includes a first sensorand a second sensor is provided. The first sensor is operable togenerate a first sensor signal indicative of a fluid pressure within theheart. The apparatus also includes a cardiac rhythm management apparatusto deliver at least one electrical stimulus to a location in the heart,where the electrical stimulus is based at least in part on the sensorsignal. The apparatus also has at least one implantable lead that iscoupled to the cardiac rhythm management apparatus. The apparatusfurther includes a signal processor, operable to generate a processoroutput indicative of a treatment, wherein the processor output is basedat least in part on the first sensor signal. The apparatus also has asignaling device, operable to generate at least two treatment signalsdistinguishable from one another by the patient, each signal indicativeof a therapeutic treatment, and where the treatment signals are based atleast in part on the processor output. The apparatus, in one embodiment,may include an electrode as part of the cardiac rhythm managementapparatus.

In a further embodiment of the invention, an apparatus for treatingcardiovascular disease is provided. The apparatus includes animplantable sensor module, operable to generate a sensor signalindicative of a fluid pressure within the left atrium of a heart. Theapparatus also has an implantable flexible lead connecting the sensormodule to an implantable housing, where the housing has a telemetryapparatus configured to communicate the sensor signal through thepatient's skin. The apparatus also includes an external telemetry deviceconfigured to communicate with the implantable apparatus. The apparatusfurther includes a signal processing apparatus operable to generate asignal indicative of an appropriate therapeutic treatment based at leastin part on the sensor signal and a patient signaling device operable togenerate at least two treatment signals distinguishable from one anotherby the patient, each treatment signal indicative of a therapeutictreatment.

In yet another embodiment, an apparatus for treating cardiovasculardisease that includes a sensor, a cardiac rhythm management apparatus, atelemetry apparatus, at least one implantable lead, a signal processor,and a signaling device is provided. The sensor is operable to generate apressure signal indicative of a fluid pressure within a left atrium of aheart. The cardiac rhythm management apparatus, the cardiac rhythmmanagement apparatus includes an electrode which is operable to deliverat least one electrical stimulus to a location in the heart. Theelectrical stimulus is based at least in part on the pressure signal.The telemetry apparatus is operable to transmit the pressure signal to alocation outside of the patient. The implantable lead is coupled to theelectrode. The signal processor is operable to generate a processoroutput indicative of a therapeutic treatment, where the processor outputis based at least in part on the pressure signal. The signaling deviceis operable to communicate the processor output to the medical patient.

In one embodiment of the invention, an apparatus for treatingcardiovascular disease in a medical patient is provided. The apparatusincludes a sensor operable to generate a pressure signal indicative ofone or more pressures, or pressure parameters within the heart, atelemetry apparatus operable to communicate the pressure signal to alocation outside of the medical patient, and a signal processor operableto generate a treatment signal indicative of a therapeutic treatment.The treatment signal is based at least in part on the pressure signal.The apparatus also includes a signaling device operable to communicatethe treatment signal to a user.

In yet another embodiment of the invention, an apparatus for treating orpreventing cardiovascular disease is provided. The apparatus includes asensing means for generating a signal indicative of one or more cardiacpressures, a means to deliver an electrical stimulus to the heart, asignal processor for generating a treatment signal indicative of atreatment, where the treatment signal is based at least in part on thepressure signal, at least one implantable lead coupled to the means todeliver an electrical stimulus, and a signaling means for communicatingthe treatment signal a user. In one embodiment, the sensing meansincludes a pressure transducer. In one embodiment, the means to deliveran electrical stimulus includes a pacemaker. In one embodiment, themeans to deliver an electrical stimulus includes a defibrillator. In oneembodiment, the signaling means includes a personal digital assistant.

In another embodiment of the invention, an apparatus for treatingcardiovascular disease in a medical patient is provided. The apparatusincludes a sensor to generate a sensor signal indicative of a fluidpressure within the left atrium and a cardiac rhythm managementapparatus to deliver an electrical stimulus to the patient. Theapparatus also includes a signal processor to generate a processoroutput indicative of a treatment, where the processor output is based atleast in part on the sensor signal, and a signaling device to generateat least two treatment signals distinguishable from one another by thepatient. Each signal indicates a therapeutic treatment and is based atleast in part on the processor output.

In one embodiment of the present invention, a method of treatingcardiovascular disease in a medical patient is provided. The methodincludes the steps of generating a sensor signal indicative of a fluidpressure within a left atrium of a heart, delivering an electricalstimulus to the heart, generating a processor output indicative of atreatment to a signaling device, and providing at least two treatmentsignals to the medical patient. The electrical stimulus is based atleast in part on the sensor signal. The processor output is based atleast in part on the sensor signal. Each treatment signal isdistinguishable from one another by the patient, and is indicative of atherapeutic treatment. At least one signal is based at least in part onthe processor output. In one embodiment, the step of delivering anelectrical stimulus includes using a pacemaker or a defibrillator.

In another embodiment, a method of treating cardiovascular disease isprovided. The method includes generating a sensor signal indicative of afluid pressure within the heart and delivering an electrical stimulus tothe patient, such as, for example, to a location in the heart. Themethod further includes providing a processor output indicative of atreatment, and providing at least two treatment signals to the medicalpatient. The electrical stimulus is based at least in part on the sensorsignal. The processor output is based at least in part on the sensorsignal. The treatment signals are distinguishable from one another bythe patient and are based at least in part on the processor output.

In a further embodiment of the current invention, a method of treatingcardiovascular disease that includes a telemetry device is provided. Themethod includes the steps of generating a sensor signal indicative of afluid pressure within a left atrium of a heart, and transmitting thesensor signal using an internal telemetry apparatus to an externaltelemetry device. The method further includes providing the sensorsignal from the external telemetry device to a signal processor,processing the sensor signal to generate a treatment signal, andcommunicating the treatment signal to a user by providing at least twosignals to the user.

In yet another embodiment of the invention, a method of determiningfluid pressure within the left atrium of a medical patient's heart isprovided. The method includes the steps of obtaining a sensor signalfrom the one or more implanted sensors in a medical patient by telemetrythrough the patient's skin, obtaining the atmospheric pressure, anddetermining an adjusted pressure signal. The adjusted pressure signal isbased at least in part upon the sensor signal and the obtainedatmospheric pressure and substantially indicates the fluid pressurewithin the left atrium of the heart relative to the atmosphericpressure.

In another embodiment of the present invention, a method of treating orpreventing cardiovascular disease in a medical patient using at leasttwo sensors is provided. The method includes generating a first sensorsignal indicative of a cardiac fluid pressure within the patient, andgenerating a second signal indicative of a physiological parameter. Themethod further includes delivering an electrical stimulus to thepatient, where the electrical stimulus is based at least in part on thefirst sensor signal. The method also includes generating a processoroutput indicative of a treatment to a signaling device, where theprocessor output is based at least in part on the first sensor signal,and providing at least two treatment signals to the patient. Thetreatment signals are distinguishable from one another by the patient,are indicative of different therapeutic treatments, and are based atleast in part on the processor output.

In another embodiment of the present invention, a method of treatingcardiovascular disease using electrical pulses is provided. The methodincludes generating a sensor signal indicative of a fluid pressurewithin a heart and delivering at least one electrical pulse to thepatient, where the pulse delivery is based at least in part on thesensor signal. The method also includes providing a processor output toa signaling device, where the processor output is indicative of atherapeutic treatment, and where the processor output is based at leastin part on the sensor signal. The method further includes providing atreatment signal to the medical patient, where the treatment signal isbased at least in part on the processor output.

In one embodiment of the invention, a method for treating cardiovasculardisease is provided. The method includes generating a pressure signalindicative of a fluid pressure within a heart and controlling thedelivery of an electrical pulse from a pacemaker to the heart. Thecontrolling step is based at least in part on the pressure signal. Themethod further includes communicating the pressure signal to a patientsignaling apparatus located at least partially external to the medicalpatient. The method also includes processing the pressure signal withthe patient signaling apparatus to determine a processor outputindicative of a therapeutic treatment, the therapeutic treatment basedat least in part on the fluid pressure within the heart, and signalingthe patient with the processor output.

In yet another embodiment of the invention, a method for treatingcardiovascular disease in a medical patient that includes the followingsteps is provided: generating a pressure signal indicative of a fluidpressure within a heart, communicating the pressure signal to locationoutside of the medical patient, generating a processor output indicativeof a therapeutic treatment, where the processor output is based at leastin part on the pressure signal, and communicating the processor outputto the medical patient.

In an alternative embodiment of the present invention, a method fortreating cardiovascular disease in a medical patient includes generatinga sensor signal indicative of a fluid pressure within the left atrium,communicating the sensor signal to an external telemetry apparatus, andgenerating a processor output indicative of an appropriate therapeutictreatment based at least in part on the sensor signal. The methodfurther includes signaling a patient with a patient signaling device.The signaling device is operable to generate at least two treatmentsignals distinguishable from one another by the patient, each treatmentsignal indicative of a therapeutic treatment, wherein each treatmentsignal is based at least in part on the processor output.

In several embodiments of the current invention, the apparatus and/ormethod for treating cardiovascular disease includes a cardiac rhythmmanagement apparatus. In one embodiment, the cardiac rhythm managementapparatus includes a pacemaker. In another embodiment, the cardiacrhythm management apparatus includes a defibrillator. In one embodiment,the cardiac rhythm management apparatus is controlled at least in partby one or more sensor signals, including, but not limited to, one ormore pressure signals.

In one embodiment, the apparatus and/or method for treatingcardiovascular disease includes an external patient advisory module. Inone embodiment, the external patient advisory module includes anexternal telemetry device, a signal processor, and a signaling device.In one embodiment, the external patient advisory module includes abarometer configured to sense atmospheric pressure.

In several embodiments of the current invention, the apparatus and/ormethod for treating cardiovascular disease includes one or more sensors.In one embodiment, the sensor includes a pressure transducer. In anotherembodiment, the sensor is in pressure communication with the leftatrium. In one embodiment, the sensor is located in the atrial septum orthe left atrium. In one embodiment, the sensor is placed in one or moreof the following locations: a right atrial appendage, a left atrialappendage, a pulmonary artery, a pulmonary vein, a pulmonary capillarywedge position, a right ventricle, a left ventricle, a right atrium, anintrathoracic space, and a central vein. In one embodiment, the sensorincludes a low compliance titanium foil. In one embodiment, the sensorincludes at least one silicon strain gauge.

In several embodiments of the current invention, the apparatus and/ormethod for treating cardiovascular disease includes one or more sensorsignals. In one embodiment, the sensor signal includes at least onepressure signal. In one embodiment, the pressure signal includes acentral venous blood pressure, a peripheral arterial blood pressureand/or a left atrial pressure. In another embodiment, the pressuresignal includes a parameter of a left atrial pressure. In oneembodiment, the parameter is selected from the group including, but notlimited to one or more of the following: mean left atrial pressure,temporally filtered left atrial pressure, heart rate, respiratoryvariation of left atrial pressure, and respiration rate. In anotherembodiment, the parameter is determined based upon at least one waveselected from the group including, but not limited to one or more of thefollowing: an a wave, a v wave, and a c wave. In yet another embodiment,the parameter is determined based upon a parameter signal selected fromthe group including, but not limited to one or more of the following: awave amplitude, a waveform rate of ascent, a waveform rate of descent,timing of a wave feature with respect to a cardiac cycle, timing of awave feature with respect to another wave feature, time differencebetween an a wave and a c wave, time difference between an a wave and av wave, and time difference between a v wave and a c wave. In oneembodiment, the parameter is determined based upon at least one descentselected from the group including, but not limited to one or more of thefollowing: an x descent, an x′ descent, and a y descent. In anotherembodiment, the parameter is determined based upon a parameter signalselected from the group including, but not limited to one or more of thefollowing: a descent amplitude, a descent rate of ascent, a descent rateof descent, timing of a descent feature with respect to a cardiac cycle,timing of a descent feature with respect to another wave feature, timedifference between an x descent and an x′ descent, time differencebetween an x descent and a y descent, and time difference between an x′descent and a y descent. In one embodiment, the parameter is independentof ambient atmospheric pressure.

In one embodiment, the sensor signal is measured during an interval. Inanother embodiment, the sensor signal is sampled in response to anevent, including but not limited to a detected event, a symptom, and/oran instruction.

In one embodiment, the apparatus and/or method for treatingcardiovascular disease further includes a sensor module. The sensormodule includes at least one sensor. In one embodiment, the sensormodule has a cylindrical shape. In one embodiment, the sensor module hasa length of about 8 mm, and a diameter of about 3 mm. In one embodiment,the sensor module has a length in a range between about 5 and 15 mm, anda diameter in a range between about 1 and 5 mm. In one embodiment, thesensor module is connected to at least one implantable lead. In anotherembodiment, the sensor module is coupled to an implantable housing withan additional lead. In one embodiment, the sensor is connected to theimplantable housing. In yet another embodiment, the sensor modulefurther includes electronics. In one embodiment, the electronicscomprise an application-specific integrated circuit (ASIC) and/or ananalog-to-digital converter. In a further embodiment, the electronicsinclude circuitry for communicating a digital signal.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease further includes a housing that is aflat oval shape. In one embodiment, the housing includes a firstdimension and a second dimension, where the first dimension is about 30mm and the second dimension is about 20 mm. In one embodiment, thehousing is implanted near a shoulder in the medical patient or in anabdominal site. In another embodiment, the housing further includes anantenna or coil. In one embodiment, the housing further includes a powersource.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease has a signaling device that is at leastpartially located in the housing. In another embodiment, the apparatusfurther includes a telemetry apparatus. In one embodiment, the telemetryapparatus is at least partially located within the housing. In oneembodiment, the housing further includes a data memory.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease has a signal processor that is locatedin an external apparatus outside of the patient's body. In oneembodiment, the external apparatus includes an external telemetryapparatus. In one embodiment, the external telemetry apparatus includes,but is not limited to, a personal digital assistant, a computer, a radiofrequency telemetry hardware module, and a coil antenna. In oneembodiment, the telemetry apparatus is operable to communicate byreflected impedance of radio frequency energy. In a further embodiment,the telemetry apparatus is operable to communicate by frequency oramplitude shifting of radio frequency energy.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes an external power source. Inone embodiment, the power source provides power through radio frequencycoupling. In one embodiment, the radio frequency includes, but is notlimited to, frequencies of about 125 kHz, about 8192 Hz, about 10.9 kHz,and about 30 kHz.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes a signal processor. The signalprocessor can be located inside the patient, on the patient, completelyoutside the patient, or partially in or on the patient. In oneembodiment, the signal processor includes a personal digital assistant.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes at least one implantable lead.In one embodiment, two leads are provided. In another embodiment, threeleads are provided. In another embodiment, more than three leads areprovided. In one embodiment, the lead includes a pacemaker lead. In oneembodiment, the lead includes a defibrillator lead. In one embodiment,the lead carries a lead signal. In one embodiment, the lead signalincludes, but is not limited to, an electrical signal, a hydraulicsignal, an optical signal, and/or an ultrasonic signal, or somecombination thereof. In one embodiment, the lead communicates the sensorsignal to the implantable housing. In one embodiment, the sensor signaland the electrical stimulus are provided by the implantable lead. Inanother embodiment, the implantable lead provides one or more powerpulses between the implantable housing and the sensor. In oneembodiment, the implantable lead provides a data signal between theimplantable housing and the sensor. In one embodiment, the data signalincludes, but is not limited to one or more of the following: a pressuresignal, a non-pressure sensing signal, a pacing signal and a programmingsignal.

In one embodiment, the implantable flexible lead is upgradable. In oneembodiment, the implantable flexible lead is configured to operate in aplurality of configurations. In one embodiment, the lead is configuredto operate in a telemetry configuration. In another embodiment, the leadis configured to operate in a telemetry configuration and a cardiacmanagement configuration. In a further embodiment, the implantableflexible lead is configured to operate in a telemetry configuration anda therapy configuration. In one embodiment, the implantable flexiblelead includes electronics that automatically senses the appropriateconfiguration.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes a signaling device. In oneembodiment, the signaling device includes a personal digital assistant.In one embodiment, the signaling device includes, but is not limited toan electrical buzzer, an alarm, and/or a telephone. In one embodiment,the signaling device provides an audible signal. In one embodiment, thesignaling device provides a visible signal.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes processor output. In oneembodiment, the processor output comprises a signal output from thesignal processor. In one embodiment, the processor output comprises asignal output to the signaling device. In one embodiment, the processoroutput includes, but is not limited to text, numerical, and/or graphicsdisplay. In one embodiment, the processor output includes, but is notlimited to codes and data.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes at least one anchor. In oneembodiment, the sensor package, or module, has anchoring mechanismsconfigured to anchor the sensor package within the atrial septum of apatient's heart. In another embodiment, one or more anchors are used toposition or hold one or more of the components described herein to asite within the patient.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease further includes an automated therapydevice. In one embodiment, the automated therapy device includes, but isnot limited to, a dynamic prescription, a drug delivery unit, and/or acardiac rhythm management apparatus. In one embodiment, the automatedtherapy device controls the AV interval of a dual chamber pacemaker. Inone embodiment, the automated therapy device is at least partiallycontrolled based upon parameters indicative of congestive heart failure.In another embodiment, the automated therapy device is at leastpartially controlled based upon parameters indicative of atrialfibrillation.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes a signal processor thatgenerates the processor output based in part on a physician's dynamicprescription. In one embodiment, the dynamic prescription includes atleast two treatment instructions corresponding to at least twophysiological conditions. In one embodiment, a physician workstation isprovided that is configured to receive and store the dynamicprescription. In another embodiment, an interface for communicating thestored dynamic prescription from the physician workstation to the signalprocessor is provided.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes the generation of at least onetreatment signal. In one embodiment, the treatment signal includes apatient instruction. In one embodiment, the treatment signal is anumerical designation. In one embodiment, two treatment signals areprovided. In one embodiment, both treatment signals are numericaldesignations. In one embodiment, the numerical designation is indicativeof a pressure measurement. In one embodiment, the treatment signal isbased at least in part on two or more physician instructions. In oneembodiment, the treatment signal is provided to a user. In oneembodiment, the user is a medical practitioner. In one embodiment the,the user is a patient. In one embodiment, the treatment signal isprovided substantially simultaneously two or more users.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease is configured to treat or preventcongestive heart failure.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes one or more additional sensorsin addition to a first sensor. In one embodiment, a range of about threesensors to about twenty sensors is provided. In one embodiment, morethan twenty sensors are provided. In one embodiment, a first sensor anda second sensor is provided. In one embodiment, the first sensor and thesecond sensor are located within a sensor module. In one embodiment, thefirst sensor is implanted within the patient and the second sensor islocated externally to the patient, either on the patient or completelyindependent of the patient. In one embodiment, the second sensormeasures a physical dimension. The physical dimension includes, but isnot limited to, a left atrial dimension, a left atrial cross-sectionalarea, a left atrial volume, a left ventricular dimension, a leftventricular cross-sectional area, and a left ventricular volume. In oneembodiment, at least one of the sensors measures a parameter thatincludes, but is not limited to, one or more of the following:electrical activity of the heart, a temperature, an atrial septumposition, a velocity of a cardiac structure, an acceleration of acardiac structure, an electrical resistance, a thoracic electricalimpedance, a respiratory tidal volume, a respiratory rate, a respiratoryminute volume, a total body weight, oxygen saturation, oxygen partialpressure, oxygen partial pressure in a left chamber of a heart, oxygenpartial pressure in a right chamber of a heart, and cardiac output. Inone embodiment, a single sensor measure two or more parameters and ismulti-functional. In one embodiment, a second sensor includes anautomated arterial pressure cuff or a weight scale.

The embodiments summarized above and described in greater detail beloware useful for the treatment of cardiovascular disease, includingcongestive heart failure (CHF). CHF is an important example of a medicalailment currently not treated with timely, parameter-driven adjustmentsof therapy, but one that the inventors believe could potentially benefitgreatly from such a strategy. Patients with chronic CHF are typicallyplaced on fixed doses of four or five drugs to manage the disease. Thedrug regimen commonly includes but is not limited to diuretics,vasodilators such as ACE inhibitors or A2 receptor inhibitors,beta-blockers such as Carvedilol, neurohormonal agents such asspironolactone, and inotropic agents usually in the form of cardiacglycosides such as, for example, Digoxin.

The inventors believe that it would be far more cost effective, and muchbetter for the patient's health, if chronic CHF could be managed andcontrolled by the routine administration of appropriate outpatient oraldrug therapy rather than by hospital treatment upon the manifestation ofacute symptoms. As with all drugs, these agents are to be taken in dosessufficient to ensure their effectiveness. Problematically, however,over-treatment can lead to bradycardia, hypotension, renal impairment,hyponatremia, hypokalemia, worsening CHF, impaired mental functioning,and other adverse conditions. Adding to the challenge of maintainingproper drug dosage is the fact that the optimal dosage will depend ondiet, particularly salt and fluid intake, level of exertion, and othervariable factors. Adding further to the problem of managing thiscondition is the fact that patients frequently miss scheduled doses byforgetting to take pills on time, running out of medications, ordeciding to stop medications without consulting their physician. It isimportant, therefore, that the patient's condition be monitoredregularly and thoroughly, so that optimal or near optimal drug therapycan be maintained. Easily obtained measures of a patient's condition areknown, such as weight, peripheral blood pressure, subcutaneous edema,temperature, and subjective measures such as fatigue and shortness ofbreath. Unfortunately, these measures either do not correlate wellenough with specific physiological states to serve as a controllingparameter for therapy, or do correlate but change too late foradjustment of oral medications to be effective. Measures that do changespecifically, sensitively, and early in response to changes in thepatient's condition are known in the art of heart failure management,but monitoring these measures is problematic in that such monitoringtypically involves inserting a catheter into the heart or central bloodvessels, therefore requiring frequent visits with a caregiver, andresulting in discomfort, inconvenience, expense, and repeated risks.

The inventors believe that it would be advantageous, therefore, ifmethods and apparatus could be devised by which an outpatient'scardiovascular status in general, and congestive heart failure inparticular, could be monitored routinely or continuously, withoutperforming an invasive procedure each time, with attendance by acaregiver only when actually required. The inventors believe that itwould be further advantageous if such methods and apparatus included theability to communicate diagnostic and treatment information promptly tothe patient himself. Such feedback would allow the patient to continueor modify his medications, as prescribed by his physician or licensedcaregiver, such that optimal therapeutic doses are achieved, generallywithout the direct intervention of his physician.

For some classes of drugs (e.g., beta blockers, digoxin, calciumantagonists, amiodorone, etc.), the optimal dose for treating heartfailure may be associated with, or exaggerate, episodes of excessivelylowered resting heart rate (bradycardia) or an inability to adequatelyincrease heart rate in response the body's demand for augmented bloodflow (cardiac output), such as occurs with exercise or stress. Thelatter condition is known as chronotropic incompetence. Inappropriatelylow heart rate causes fatigue, poor exercise tolerance, and in the worstcases, deteriorating kidney function, low blood pressure and shock. Therisk of these potentially serious complications limits the dose of thesebeneficial drugs that can be safely prescribed.

It would be additionally advantageous, therefore, if the methods andapparatus for monitoring a patient's cardiovascular status in general,and congestive heart failure in particular, and notifying the patient tocontinue or modify his medications, could also provide electronicpacemaker stimulation of the heart as needed to prevent bradycardia orchronotropic incompetence as a side effect of these drugs.

Several embodiments of the present invention provides these advantages,along with others that will be further understood and appreciated byreference to the written disclosure, figures, and claims includedherein.

BRIEF DESCRIPTION OF THE DRAWINGS

The structure and operation of the invention will be better understoodwith the following detailed description of embodiments of the invention,along with the accompanying illustrations, in which:

FIG. 1 depicts apparatus suitable for practicing at least one embodimentof the invention.

FIG. 2 depicts an implantable apparatus suitable for practicing anotherembodiment of the invention.

FIG. 3 is a schematic of one embodiment of the electronics locatedwithin the implantable housing of the implantable apparatus illustratedin FIG. 2.

FIG. 4 is a system for treating cardiovascular disease.

FIG. 5 is a block diagram of an external patient advisor/telemetrymodule for use in one embodiment of the present invention.

FIGS. 6A-6C provide a list of examples by which signals may beinterpreted to facilitate diagnosis, prevention and treatment ofcardiovascular disease.

FIG. 7 shows a table of cardiac and non-cardiac diagnostic statesderivable from measurements at the intra-atrial septum.

FIG. 8 shows the flexible lead of FIG. 13. The sheath has been withdrawnto deploy the proximal distal anchors on the right and left atrial sidesof the atrial septum, and a pressure sensing transducer is in fluidcontact with the patient's left atrium.

FIG. 9 depicts a method for anchoring a flexible electrical lead withinthe patient's heart.

FIG. 10 is a schematic sectional view of a patient's heart illustratingan atrial septal puncture for implanting one embodiment of the currentinvention.

FIG. 11 shows another method for anchoring a lead within the heart,which includes a helical screw for advancement into the patient's atrialseptum.

FIG. 12 shows the apparatus depicted in FIG. 11, with a pressure sensingtransducer in place in the patient's left atrium.

FIG. 13 is a schematic sectional view of a patient's heart showing apart of an embodiment of the invention positioned therein.

FIG. 14 shows the flexible lead of FIG. 15 and FIG. 16, with a pressuresensing transducer in place inside the patient's left atrium.

FIG. 15 depicts a flexible lead including deployable anchors carriedinside a removable sheath and placed through the atrial septum.

FIG. 16 shows the flexible lead of FIG. 15 with the sheath withdrawn todeploy the anchors on opposite sides of the atrial septum.

FIG. 17 shows the correlation between the pulmonary capillary wedgepressure (PCW) referenced to atmospheric pressure (abscissa) and thedifferential pressure between the right atrium and PCW (PCW-RA).

FIG. 18 illustrates typical normal pressure tracings.

FIG. 19 provides a table of normal hemodynamic values.

FIG. 20 shows a combination of one embodiment of the present inventionwith an implantable cardiac pacemaker, in which the sensor is a leftatrial pressure sensor implanted in the intra-atrial septum, and thepacemaker leads are entirely separate from the pressure sensor lead.

FIG. 21 shows the relationships between the electrocardiogram and theleft atrial pressure tracing.

FIG. 22 is a sensor package or module in accordance with one embodimentof the present invention.

FIG. 23 is another sensor package or module in accordance with anotherembodiment of the present invention.

FIG. 24 is a pulse timing diagram showing one embodiment for sensing oneor more physiological parameters and performing cardiac pacing using atwo-conductor digital sensor/pacemaker lead.

FIG. 25 is a schematic showing one embodiment of circuitry that providesboth pacing and physiological monitoring over a two-conductor pacemakerlead.

FIGS. 26A-D are schematics showing circuitry within a sensor module inaccordance with another embodiment of the present invention.

FIG. 27 is a schematic diagram depicting digital circuitry suitable foruse in one embodiment of the invention.

FIG. 28 is an implantable housing in accordance with one “Stand-Alone”embodiment of the invention.

FIG. 29 is an implantable housing in accordance with one “CRMCombination” embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

In one embodiment of the present invention an apparatus for treatingcardiovascular disease in a medical patient is provided. The apparatusincludes a sensor, an implantable housing, at least one implantablelead, a signal processor, and a signaling device. In one embodiment, theapparatus is a physiologically optimized dosimeter (POD™), such as theHEARTPOD™ device developed by the Applicant. Cardiovascular disease, asused herein, shall be given its ordinary meaning, and shall also includehigh blood pressure, diabetes, coronary artery disease, valvular heartdisease, congenital heart disease, arrthymia, cardiomyopathy, and CHF.

In one embodiment of the present invention, a method of treatingcardiovascular disease in a medical patient is provided. The methodincludes the steps of generating a sensor signal indicative of a fluidpressure within a left atrium of a heart, delivering an electricalstimulus to the heart, generating a processor output indicative of atreatment to a signaling device, and providing at least two treatmentsignals to the medical patient. The electrical stimulus is based atleast in part on the sensor signal. The processor output is based atleast in part on the sensor signal. Each treatment signal isdistinguishable from one another by the patient, and is indicative of atherapeutic treatment. At least one signal is based at least in part onthe processor output. In one embodiment, the step of delivering anelectrical stimulus includes using a pacemaker or a defibrillator.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes one or more sensors. In oneembodiment, the sensor is designed to generate a sensor signal that isindicative of a fluid pressure within the left atrium of the patient'sheart. As described herein, fluid pressure within the left atrium of apatient's heart is an excellent indicator for quantifying the severityof congestive heart failure, and for assessing the effectivity of drugtherapy for treating congestive heart failure. A measurement of thefluid pressure within the left atrium of a patient's heart can be usedfor other clinical purposes as well, as described in greater detailbelow.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes one more housing units. In oneembodiment, the implantable housing of the apparatus includes a cardiacrhythm management (CRM) apparatus, such as, for example, a pacemaker, ora defibrillator. The implantable housing generally includes varioussubassemblies for control, operation, processing, and communication.However, in some embodiments, any one or more of control, operation,processing, and communication may be performed by an assembly, or modulethat is not included with the implantable housing. In one embodiment,when implanted in the patient, the implantable housing contains a coilantenna and electronics to provide reflected impedance communicationswith an external device. However, the implantable housing may besubsequently accessed, and the coil antenna may be removed and replacedwith a CRM. The implantable housing and electronics may include aninterface that permits such interchangeability of components within theimplantable housing without requiring explantation of the remainingcomponents of the congestive heart failure treatment apparatus. Theseand additional embodiments of the implantable housing as well as theapparatus are provided in greater detail below.

In one embodiment, the lead couples the sensor to the implantablehousing, and provides an electrical conduit for the transmission of thesensor signal from the sensor to the housing. In other embodiments,however, as described in greater detail below, the lead provides anelectrical stimulus, such as, for example, an electrical pulse, to alocation in the heart, as determined by the CRM apparatus. In someembodiments, the electrical stimulus and the sensor signal aretransmitted through the same lead, and in other embodiments, more thanone lead is provided. In yet another embodiment, energy or power istransmitted from the implantable housing through the lead to a distalmodule that may contain a CRM, sensor, and electronics necessary tocontrol the congestive heart treatment apparatus. These and otherembodiments are described in greater detail below.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes one or more signal processors.In one embodiment, the signal processor determines a processor outputthat is indicative of an appropriate therapeutic treatment in responseto the pressure-indicative signal provided by the sensor. The processoroutput is provided to a signaling device, which provides an appropriatetreatment signal to the medical patient. The term “processor output” asused herein shall be given its ordinary meaning and shall also meanoutput from a signal processor and/or input to a signaling device, andshall include, but not be limited to, signals, including analog,digital, and/or optical signals, data, code, and/or text. The treatmentsignal may be provided by, for example, vibrating a signaling devicelocated within the implantable housing. Alternatively, the treatmentsignal may be generated within the implantable housing and transmittedto a signaling device located external to the patient, such as apersonal digital assistant (PDA). In another embodiment, the sensorsignal is transmitted to an external device, such as, for example, aPDA, which includes a processor and signaling device to generate aprocessor output and provide a treatment signal to the patient. Theseand other embodiments are described in greater detail below.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes one or more signaling devices.In one embodiment, the signaling device includes a buzzer, an alarm, adisplay, a computer, a telephone, or a PDA, such as a PALM PILOT™ (PalmComputing, Inc.), or a HANDSPRING VISOR® (Handspring, Inc.). Thesignaling device may be operable to generate at least two treatmentsignals distinguishable from one another by the patient. In oneembodiment, each signal is indicative of a different therapeutictreatment. The treatment signal may be an electrical pulse, a vibration,a noise, audio or visual data, including, but not limited to,instructions on a display screen or light emitting diodes. In oneembodiment, the at least two treatment signals may include two numericalvalues or designations, a numerical value and an electrical pulse orvibration, multiple vibrations of varying amplitudes, durations, orfrequencies, or any combination of two or more of any of the treatmentsignals described herein. In one embodiment, the signaling device is aPDA that displays an instruction, such as “take medication,” “rest,” or“call Doctor”. These and other embodiments are described in greaterdetail below.

I. THE SYSTEM A. Stand-Alone System

FIG. 1 shows an apparatus for treating cardiovascular disease, such ascongestive heart failure, which includes an implantable module 5 inaccordance with one embodiment of the invention. The implantable module5 includes a housing 7 and a flexible, electrically conductive lead 10.The lead 10 is connectable to the housing 7 through a connector 12 thatmay be located on the exterior of the housing. In one embodiment, thehousing 7 is outwardly similar to the housing of an implantableelectronic defibrillator and/or pacemaker system. Defibrillator andpacemaker systems are implanted routinely in medical patients for thedetection and control of tachy- and bradyarrhythmias. The flexible lead10 is also generally similar to leads used in defibrillator andpacemaker systems, except that a compact sensor package 15 is disposedat or near the distal end 17 of the lead 10, the opposite end from theconnector 12 on the housing 7. The sensor package 15 contains sensors tomeasure one or more physical parameters. An electrical signal or anotherform of signal indicative of these physical parameters is thentransmitted along the lead 10 through the connector 12 and to thehousing 7. The housing 7 includes a signal processor (not shown) toprocess the signal received from the sensor package 15 via the lead 10.In addition, the housing 7 may include telemetry or signaling devices(not shown), to either communicate with an external device, or signalthe patient, or both. The elements inside the housing 7 may beconfigured in various ways, as described below, to communicate to thepatient a signal, such as a treatment signal, indicative of anappropriate therapy or treatment based at least in part on one or moreof the measured physical parameters.

FIG. 2 shows another embodiment in which the sensor package or module 15has distal 68 and proximal 70 anchoring mechanisms configured to anchorthe sensor package 15 within the atrial septum of a patient's heart.FIG. 2 shows one embodiment of the implanted internal module 5, in whichthe implanted internal module 5 includes a physiologic sensor package ormodule 15. The physiologic sensor package 15 includes one or moresensors (not shown) and their accompanying electronics (not shown). Theimplanted module 5 also includes a flexible lead 10. The flexible lead10 has a distal end 17 and an indifferent electrode 14. A header orconnector 12 connects the flexible lead 10 and housing 7 of theimplanted module 5. The housing 7 contains electronics (not shown) andother components (not shown) for communicating with an external module(not shown). One embodiment showing the contents of the housing 7 isillustrated in FIG. 3.

As shown in FIG. 3, in one embodiment housing 7 includes a power supply153, a CRM system 159, and a signal processing and patient signalingmodules 157. The CRM system 159 is configured to provide an electricalstimulus, such as a pacing signal, to the patient's heart, and receive asensor signal from implanted sensors (not shown). In one embodiment, theCRM system 159 is configured to control a defibrillator. The signalprocessing module 157 is coupled to at least one sensor that provides asignal indicative of the fluid pressure within the left atrium of theheart. The signal processing module 157 may also be configured tocontrol distally implanted CRM components, or a sensor package ormodule, as described in greater detail herein.

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease at least one housing. In one embodiment,the housing includes a shape that is flat and oval. In anotherembodiment, the shape is cylindrical, rectangular, elliptical, orspherical. One of skill in the art will understand that a variety ofother shapes suitable for implantation can also be used. In oneembodiment, the housing is about 20 mm by about 30 mm, about 10 mm byabout 20 mm, or about 5 mm by about 10 mm. In one embodiment, thehousing is about 5 mm thick. In one embodiment, the housing is implantedin the medical patient near the shoulder. In another embodiment, thehousing has dimensions suitable for containing at least some componentsfor controlling, powering and/or communicating with a pacemaker andsuitable for implantation inside of the body, as is well known to thoseof skill in the art. In another embodiment, the housing includes: anantenna, or a coil; a power source, including but not limited to abattery or a capacitor; a signal processor; a telemetry apparatus; adata memory; or a signaling device. In one embodiment, the apparatus ispowered by an external power source through inductive, acoustical, orradio frequency coupling. In one embodiment, power is provided usingelectromagnetic emissions emitted from an electrical coil locatedoutside the body. In one embodiment, power and data telemetry areprovided by the same energy signal. In another embodiment, an electricalcoil is implanted inside the body at a location under the skin near thepatient's collarbone. In another embodiment, an electrical coil isimplanted inside the patient's body at other locations. For example, inone embodiment, the coil is implanted under the skin in the lowerabdomen, near the groin. One of skill in the art will understand thatthe device can be implanted in a variety of other suitable locations.

As described above and in other embodiments herein, a system fortreating cardiovascular disease in a medical patient may include atleast one physiological sensor used to generate a signal indicative of aphysiological parameter on or in the patient's body. The system includessignal processing apparatus operable to generate a signal, such as aprocessor output, indicative of an appropriate therapeutic treatment,which is based upon the signal generated by the physiological sensor. Inone embodiment, the system also includes a patient signaling device,which is used to communicate the signal indicative of the appropriatetherapeutic treatment, such as a treatment signal, to the patient.

In one embodiment, the physiological sensor is a pressure transducerthat is positioned to measure pressures within the patient's leftatrium. Signals from the pressure sensor are monitored continuously orat appropriate intervals. Information is then communicated to thepatient corresponding to appropriate physician-prescribed drugtherapies. In one embodiment, the information is the treatment signal.In many cases, the patient may administer the drug therapies to him orherself without further diagnostic intervention from a physician.

FIG. 4 shows one embodiment of a system for treating cardiovasculardisease 9. The system 9 includes an implantable module 5, such as thatdescribed with reference to FIG. 2, and an external patient advisorymodule 6, such as that described below with reference to FIG. 5. Duringsystem 9 operation, radio frequency signals are carried by a lead 10between a pressure sensor package 15 located near the distal end 17 ofthe lead 10, and a housing 7 of an implantable module 5. The lead 10includes an indifferent electrode 14. The circuitry inside the housing 7includes an antenna coil (not shown). In this embodiment, signals arecommunicated between the implantable module 5 and an external device,such as a patient advisory module 6, via the antenna coil of the housing7 and a second external coil (not shown) coupled to the external device6.

In one embodiment, the housing 7 contains a battery (not shown) thatpowers the implantable device 5. In another embodiment, the implanteddevice 5 receives power and programming instructions from the externaldevice 6 via radio frequency transmission between the external andinternal coils. The external device 6 receives signals indicative of oneor more physiological parameters from the implanted device 5 via thecoils as well. One advantage of such externally powered implantabledevice 5 is that the patient will not require subsequent surgery toreplace a battery. In one embodiment of the present invention, power isrequired only when the patient or the patient's caregiver initiates areading. In other situations, where it is desired to obtainphysiological information continuously, or where it is desired that theimplanted device 5 also perform functions with higher or more continuouspower requirements, the housing 7 may also contain one or morebatteries. As described below, the housing 7 may also contain circuitryto perform additional functions that may be desirable.

FIG. 5 shows one embodiment of a patient advisory module 6. In oneembodiment, the patient advisory module 6 includes a palm-type computerwith added hardware and software. Referring to FIG. 5, a patientadvisory module 6 includes a radio frequency telemetry module 164 withan associated coil antenna 162, which is coupled to a processing unit166. In one embodiment, the processing unit 166 includes a palm-typecomputer, or personal digital assistant (PDA), as is well known to thoseof skill in the art. In one embodiment, the patient advisory module 6powers the implanted apparatus (not shown) with the telemetry hardwaremodule 164 and coil antenna 162. In another embodiment, the patientadvisory module 6 receives physiological signals from the implantedapparatus by wireless telemetry through the patient's skin.

The patient advisory module 6 may include an RF unit 168 and a barometer112 for measuring the reference atmospheric pressure. In one embodiment,the RF unit 168 and barometer are located within the telemetry module164, although they can be integrated with the processing unit 166 aswell. The signal processing unit can be used to analyze physiologicsignals and to determine physiologic parameters. The patient advisorymodule 166 may also include data storage, and a sub-module that containsthe physician's instructions to the patient for therapy and how to altertherapy based on changes in physiologic parameters. The parameter basedphysician's instructions are typically referred to as “the dynamicprescription,” or DynamicRx™ (Savacor, Inc.). The instructions arecommunicated to the patient via the signaling module 166, or anothermodule. The patient advisory module 166 is located externally and usedby the patient or his direct caregiver. It may be part of systemintegrated with a personal digital assistant, a cell phone, or apersonal computer, or as a Stand-Alone device. In one embodiment, theexternal patient advisory module comprises an external telemetry device,a signal processing apparatus, and a patient signaling device. In oneembodiment, the patient advisory module is operable to obtain the sensorsignal from the implantable sensor by telemetry through the patient'sskin; obtain the atmospheric pressure from the barometer; and adjust thesensor signal indicative of a fluid pressure based at least in part uponthe atmospheric pressure obtained by the barometer so that the adjustedsensor signal indicates the fluid pressure within the left atrium of theheart relative to the atmospheric pressure.

In one embodiment, the physiologic signals are analyzed and used todetermine adjustable prescriptive treatment instructions that have beenplaced in the patient advisory module 6 by the patient's personalphysician. Communication of the prescriptive treatment instructions tothe patient may appear as written or graphic instructions on a displayof the patient advisory module 6. These treatment instructions mayinclude what medications to take, dosage of each medication, andreminders to take the medications at the appropriate times. In oneembodiment, the patient advisory module 6 displays otherphysician-specified instructions, such as “Call M.D.” or “Call 911” ifmonitored values become critical.

A third module of this embodiment is designed for physician use. Thethird module is used to program the dynamic prescription and communicateit or load it into the patient advisory module 166. The third module mayalso contain stored data about the patient, including historical recordsof the physiologic signals and derived parameters transmitted from thepatient implant and signaling modules. The third module may alsocommunicate with external databases. In one embodiment, the third moduleis a physician input device, and includes a personal computer, a PDA, atelephone, or any other such device as is well known to those of skillin the art.

In one embodiment, the second module (e.g., the patient advisory module166) is in the form of one or more implants.

In one embodiment of the present invention, the first implant module(such as, for example, implantable module 5 of FIG. 1 and FIG. 2) mayalso contain an implant therapy unit, or ITU. The ITU generates anautomatic therapy regime based upon the programmed dynamic prescription.The therapy may include, but is not limited to, a system for releasingbioactive substances from an implanted reservoir, a system forcontrolling electrical pacing of the heart, and controllers forventricular or other types of cardiac assist devices. For example, inone embodiment the sensor package is placed across the intra-atrialseptum and serves as the atrial lead of a multichamber pacemaker. Thephysiologic sensor information is used to adjust pacing therapy suchthat pacing is performed only when needed to prevent worsening heartfailure. One skilled in the art will appreciate that many systems ordevices that control the function of the cardiovascular system may beused in accordance with several embodiments of the current invention.

In one embodiment of the invention, the advisory module 6 is programmedto signal the patient when it is time to perform the next cardiac statusmeasurement and to take the next dose of medication. It will berecognized by those skilled in managing CHF patients that these signalsmay help the many patients who have difficulty taking their medicationon schedule. Although treatment prescriptions may be complex, oneembodiment of the current invention simplifies them from the patient'sperspective by providing clear instructions. To assure that informationregarding the best treatment is available to physicians, professionalcardiology organizations such as the American Heart Association and theAmerican College of Cardiology periodically publish updated guidelinesfor CHF therapy. These recommendations can serve as templates for thetreating physician to modify to suit individual patient requirements. Inone embodiment, the device routinely uploads data to the physician orclinic, so that the efficacy of the prescription and the response toparameter driven changes in dose can be monitored. This enables thephysician to optimize the patient's medication dosage and otherimportant treatments without the physician's moment-to-momentintervention.

In various embodiment of the invention, a device and method fordynamically diagnosing and treating cardiovascular illness in a medicalpatient are provided. In one embodiment, at least one physiologicalsensor is used to generate a signal indicative of a physiologicalparameter. In another embodiment, signal processing apparatus operableto generate a signal indicative of an appropriate therapeutic treatmentbased, at least in part, upon the signal generated by the physiologicalsensor, is also provided. In another embodiment a patient signalingdevice used to communicate the signal indicative of the appropriatetherapeutic treatment to the patient is provided as well.

In one embodiment, a device and method for continuously or routinelymonitoring the condition of a patient suffering from chroniccardiovascular disease are provided. As will be described in detailbelow, a system incorporating various embodiments of the inventionmonitors various physiologic parameters, such as the patient's leftatrial pressure. Depending upon the magnitude of or changes in thispressure, for example, the system communicates a signal to the patientindicative of a particular course of therapy appropriate to manage orcorrect, as much as possible, the patient's chronic condition. In someembodiments, physician instructions and automated therapy are provided.

In one embodiment, the physiological sensor generates a signalindicative of a physiological parameter on or in the patient's body. Inone embodiment, the signal processing apparatus generates a signalindicative of an appropriate therapeutic treatment based at least inpart upon the signal generated by the physiological sensor. The patientsignaling device may generate signals indicative of therapeutictreatments or courses of action the patient can take to manage orcorrect, as much as possible, the patient's condition.

In one embodiment, this method includes the steps of implanting one ormore physiological sensors substantially permanently within the patient,operating the physiological sensor to generate a signal indicative of aphysiological parameter, processing this physiological signal togenerate a signal indicative of an appropriate therapeutic treatment,and communicating the appropriate therapeutic treatment to a user. Inone embodiment, the user includes, but is not limited to, the patient, acaregiver, a medical practitioner or a data collection center.

In another embodiment, the system is combined with or incorporated intoa CRM system, with or without physiologic rate control, and with orwithout backup cardioversion/defibrillation therapy capabilities.

In one embodiment, at least one indication of congestive heart failure(CHF) is monitored. Elevated pressure within the left atrium of theheart is the precursor of fluid accumulation in the lungs, which resultsin signs and symptoms of acute CHF. Mean left atrial pressure in healthyindividuals is normally less than or equal to twelve millimeters ofmercury (mm Hg). Patients with CHF that have been medically treated andclinically “well compensated” may generally have mean left atrialpressures in the range from 12 to 20 mm Hg. Transudation of fluid intothe pulmonary interstitial spaces can be expected to occur when the leftatrial pressure is above about twenty-five mm Hg, or at somewhat morethan about thirty mm Hg in some patients with chronic CHF. Pulmonaryedema has been found to be very reliably predicted by reference to leftatrial pressures and less well correlated with conditions in any otherchamber of the heart. Thus, the methods and apparatus of severalembodiments of the invention may prove very useful in treating andpreventing pulmonary edema and other adverse conditions associated withCHF. Pressure in the pulmonary veins, pulmonary capillary wedgeposition, and left ventricular end diastolic pressure (LVEDP) aregenerally indicative of left atrial pressure and are commonly used assurrogates of LAP. There are, however, specific conditions, that arewell known to those skilled in the art, including cardiologists andphysiologists, where these surrogates vary substantially from LAP andmay be less predictive of impending heart failure. One example of such acondition is mitral valve stenosis where pulmonary edema developsdespite a normal LVEDP due to a significant pressure gradient across themitral valve. Other surrogate pressures that also, on specific occasion,indicate LAP include, but are not limited to: the pulmonary arterydiastolic (PAD) or algorithms that estimate PAD from the rightventricular waveform, the right ventricular end diastolic, and the rightatrial pressure.

An embodiment of the invention includes a permanently implanted devicedesigned to define the presence of worsening CHF hours to days beforethe onset of symptoms and to provide for early preventative treatmentaccording to the physician's individualized prescription. As such, anembodiment of the invention includes an integrated patient therapeuticsystem that determines therapeutic dosages for an individual patientbased at least in part on internal physiologic signals. In anotherembodiment, the system consists of a small implantable sensor device andan external patient advisory module comprising a personal data assistant(PDA) and a telemetry module. The sensor system may be implanted intothe patient's left atrial chamber by a transseptal catheterizationprocedure. There are already several thousand physicians in the U.S. andabroad with the experience and skills required for such deviceimplantation. The implantation procedure can be performed on anoutpatient basis in a hospital's cardiac catheterization laboratory. Theimplant may alternatively be placed at the time of open-heart orminimally invasive valve or bypass surgery where the surgeon, underdirect or laparoscopic vision, positions the device in the left atrium,left atrial appendage, or an adjacent pulmonary vein.

In one embodiment, the sensor system measures a left atrial pressurewaveform, core body temperature and a cardiac electrogram, such as theintra cardiac electrogram (IEGM). Elevated left atrial pressure is themost accurate predictor of impending CHF, often preceding clinicalsymptoms by hours to days. Other embodiments of the left atrial pressurewaveform may be used to diagnose a number of conditions, as listed inFIGS. 6A-6C. Core temperature is often depressed in acute CHF, butelevated prior to the development of fever in response to an infection,making core temperature a useful parameter for differentiating betweenthese common conditions with similar symptoms but which requiredifferent treatments. The intracardiac electrogram may be useful indiagnosing arrhythmias and precipitating causes of worsening CHF.

FIG. 7 shows how left and right atrial pressure measurements may becombined with IEGM and core temperature measurement to diagnose a numberof cardiac and non-cardiac conditions. The list of diagnostic states inFIG. 7 is exemplary, and by no means exhaustive of all the potentialdiagnostic states definable by the given parameters. Multiple states canexist simultaneously, for example, moderate CHF and rapid atrialfibrillation. The measured parameters can be used over large populationsto define the probability of any given diagnostic state. Each diagnosticstate may have a unique treatment. For example, mild CHF may be treatedby increasing diuretic therapy, whereas rapid atrial fibrillation istreated with a drug that blocks AV node conduction. Many of the stateslisted can contribute to worsening CHF.

1. Implantation and Anchoring

a. Placement and Anchoring in the Left Atrium

In one embodiment, such as that illustrated in FIG. 8, an implantabledevice is implanted percutaneously in the patient by approaching theleft atrium 36 through the right atrium 30, penetrating the patient'satrial septum 41 and positioning one or more physiological sensors 15 inthe atrial septum 41, on the septal wall of the left atrium 36, orinside the patient's left atrium 36. FIG. 8 shows an embodiment in whicha sensor package 15 is deployed across the atrial septum 41. The sensorlead 10 is coupled to a physiological sensor or sensors 15 and anchoringapparatus at the lead 10 distal end 17. The anchoring apparatus includesa distal foldable spring anchor 68 that expands in diameter upon releaseand is located at or near the distal tip of the sensor 15, and aproximal foldable spring anchor 70. The distal and proximal anchors 68,70 are sufficiently close together that when deployed the two anchors68, 70 sandwich the intra-atrial septum 41 between them, thus fixing thesensor/lead system to the septal wall. The intra-atrial septum 41 istypically between about 1 and about 10 mm thick. In one embodiment, theanchors 68, 70 are made of a highly elastic biocompatible metal alloysuch as superelastic nitinol. The lead 10 may contain a lumen that exitsthe lead 10 at its proximal end. A stiffening or bending stylet can beinsert in the lumen to aid in passage of the sensor(s) and lead 15, 10.After a transseptal catheterization has been performed, a sheath/dilatorsystem of diameter sufficient to allow passage of the sensor/lead systemis placed from a percutaneous insertion site over a guidewire until thedistal end of a sheath 67 is in the left atrium 36. Left atrial positioncan be confirmed under fluoroscopy by contrast injection, or by thepressure waveform obtained when the sheath 67 is connected to a pressuretransducer. To aid the procedure, the sheath 67 may include a proximalhemostasis valve to minimize air entrainment during device insertion. Aside port with a stopcock is useful to aspirate any remaining air and toinject radiographic contrast material. Additionally, later sheath 67removal may be facilitated by using a “peel-away” type of sheath. Thesefeatures of vascular sheaths are commercially available and well know tothose familiar with the art. With the spring anchors 68, 70 folded andforming a system with minimal diameter, the system is loaded into thesheath 67 and advanced until the distal spring 68 just exits the sheath67 in the left atrium 36 and is thus deployed to its sprung diameter.The sheath 67 is carefully withdrawn without deploying the proximalanchor 70 and the sheath 67 and sensor/lead system are withdrawn as aunit while contrast is injected through the sheath 67 around the sensorlead until contrast is visible in the right atrium 30. The proximalsheath 67 is further withdrawn, allowing the proximal anchor 70 tospring to its unloaded larger diameter, thus fixing the distal portionof the sensor lead to the septum 41.

It will also be apparent that, in several embodiments, a similarsensor/lead system can be inserted through an open thoracotomy or aminimally invasive thoracotomy, with the anchoring system fixating thesensor/lead to a location such as the free wall of the left atrium, theleft atrial appendage, or a pulmonary vein, all of which provide accessto pressures indicative of left atrial pressure.

In one alternative embodiment, a flexible lead 10 is partially advancedinto a pulmonary vein 50 connected to the left atrium 36 such that oneor more physiological sensors 15 disposed on the flexible lead 10 apredetermined distance from its distal end 17 are positioned within theleft atrium 36 or the pulmonary vein 50, as shown in FIG. 9. In anotherembodiment, the distal portion 17 of the flexible lead 10 is partiallyadvanced into the left atrial appendage such that anchoring apparatuswill be occlusive of the appendage, for example as taught by Lesh et al.in U.S. Pat. No. 6,152,144, incorporated by reference herein. Thephysiologic sensors 15 are positioned on the lead 10 proximal to theocclusive anchors so that they sense conditions in the left atrium.

In other embodiments, such as those shown in FIG. 12 and FIG. 14, afirst lead component 53 includes an anchoring apparatus, for example, ahelical screw 57, which is advanced to the atrial septum 41. Theanchoring apparatus is deployed to anchor the first lead component 53into the patient's atrial septum 41. A second lead component 60 includesa physiological sensor, for example, a pressure transducer 62, which isadvanced along the first lead component 53 until the second leadcomponent 60 is in a position such that the physiological sensor ispositioned within the patient's left atrium 36.

b. Implantation in the Left Atrium

Referring to the embodiment depicted in FIG. 8, the system is implantedthrough the left atrial septum 41 such that the pressure sensor 15 isexposed to the pressure in the left atrial chamber 36 of the heart. Theleft atrial septum 41 can be accessed from the right atrium 30 throughthe inferior or superior vena cava 35, 28, as is well known to thoseskilled in the arts of, for example, pacemaker lead placement, catheterablation for control of arrhythmias originating in the left atrium orpulmonary veins, percutaneous repair of the mitral valve, andpercutaneous closure of an atrial septal defect. In one embodiment, theflexible lead 10 and pressure transducer 15 are anchored to the atrialseptum 41. This placement can be achieved using vascular accesstechniques that are well-known to those familiar with the performance ofinvasive cardiovascular procedures, in particular, interventionalcardiologists, electrocardiologists, and cardiovascular surgeons. Theseprocedures are commonly performed with the aid of visualizationtechniques, including standard fluoroscopy, cardiac ultrasound, or otherappropriate visualization techniques used alone or in combination.

Access to the central venous circulation may be achieved by use of thestandard Seldinger technique through the left or right subclavian vein,the right or left internal jugular vein, or the right or left cephalicvein. Alternatively, access may be made via the Seldinger technique intothe right femoral vein. In either case, a Brockenbrough catheter andneedle are used to pierce the atrial septum 41 for access to the leftatrium 36, as described below.

i. Superior Venous Access (Subclavian or Internal Jugular Vein)

FIG. 10 provides a schematic sectional view of the patient's heart 33and shows the apparatus used to access the left atrium 36. FIG. 10depicts an access assembly 18 comprising a Brockenbrough catheter 20inside a sheath 22, with a flexible guidewire 25 residing within theBrockenbrough catheter 20. As FIG. 10 indicates, the access assembly hasbeen placed through the superior vena cava 28 into the right atrium 30of the heart 33. FIG. 10 also shows the inferior vena cava 35, the leftatrium 36, the right ventricle 37, the left ventricle 40, the atrialseptum 41 that divides the two atria 30, 36, and the valves 42 betweenthe right atrium 30 and right ventricle 37, and the left atrium 36 andleft ventricle 40. The reader will appreciate that the view of FIG. 10is simplified and somewhat schematic, but that nevertheless FIG. 10 andthe other views included herein will suffice to illustrate adequatelythe placement and operation of an embodiment of the present invention.

ii. Placement of the Lead

With the access assembly 18 in place within the right atrium 30, theBrockenbrough catheter 20 is used to pierce the atrial septum 41 byextending the Brockenbrough needle (not shown) through the atrial septum41 into the left atrium 36. In the figures, the atrial septum 41 hasbeen pierced by the needle, the catheter 20 has been advanced over theneedle, and the needle has been withdrawn from the catheter 20, leavingthe catheter 20 in place inside the left atrium 36. Optionally, aguidewire 25 may be advanced through the needle into the left atrium 36before or after advancing the catheter 20, or it may be placed into theleft atrium 36 through the catheter 20 alone after the needle has beenwithdrawn. A lead placement procedure is described above.

As indicated by the arrows 45 in FIG. 10, the sheath 22 may extend intothe left atrium 36, or it may remain on the proximal side of the atrialseptum 41 within the right atrium 30. FIG. 10 shows the guidewire 25extended from the end of the Brockenbrough catheter 20 to securecontinuous access into the left atrium 36. As depicted therein, theguidewire 25 has a curled, “pig-tail” style distal tip 48 to bettersecure the guidewire 25 within the left atrium 36 and to safeguardagainst inadvertent withdrawal through the atrial septum 41.Alternatively, a “floppy tip” guide wire may be used, which can besafely advanced well into one of the pulmonary veins, again to safeguardagainst inadvertent withdrawal through the atrial septum 41. Once theguidewire 25 is securely in place in the left atrium 35, theBrockenbrough catheter 20 may be withdrawn so that the flexible lead 10may be placed through the peel-away sheath 22.

With the guidewire 25 securely in place with its distal tip 48 insidethe left atrium 36, the flexible lead 10 may be advanced into the leftatrium 36. The flexible lead 10 might itself include a central lumenconfigured to receive the proximal end of the guidewire 25, therebyallowing the flexible lead 10 to be advanced down the guidewire 25toward the left atrium 36. More commonly, an exchange catheter, whichmay be in the form of a peel-away sheath 22, will be advanced down theguidewire 25 and placed into the left atrium 36, the guidewire 25 maythen be withdrawn, after which the flexible lead 10 will be advanceddown the exchange catheter and into position.

In one embodiment, a peel-away sheath 22 is used to allow the sheath tobe removed once the distal end of the lead 10 is implanted. Thepeel-away feature is not used if the proximal end of the lead 10 isdetachable from the coil housing assembly (described above). In thiscase, a non-peel-away sheath with proximal hemostasis valve and sideport as described above can be used, and simply slid off the proximalend of the lead 10 prior to attaching the lead 10 to the coil/housingassembly.

iii. Anchoring the Sensor and Lead

Once the pressure transducer 15 of the flexible lead 10 is positionedwithin the left atrium 36, the lead 10 should be anchored in place toensure that the pressure transducer 15 stays reliably and permanently inthe desired location.

One method for anchoring the flexible lead 10 in place is depicted inFIG. 9, which is a somewhat schematic depiction of the major structuresof the heart. FIG. 9 shows the four pulmonary veins 50 that connect tothe left atrium 36. In the particular apparatus depicted in FIG. 9, theflexible lead 10 includes a pressure transducer 15 located on the bodyof the lead 10 a predetermined distance proximal of the distal end 17 ofthe lead 10.

Referring back to FIG. 9, the distal end 17 of the flexible lead 10 inthis embodiment can be bent by the operator in much the same way as adistal tip such as might be found on a steerable angioplasty guidewireor another similar device. This feature assists the operator in steeringthe flexible lead 10 into a selected one of the pulmonary veins 50, withthe pressure transducer 15 disposed within the interior space of theleft atrium 36, or even within the pulmonary vein itself. Placement ofthe pressure transducer 15 within the pulmonary vein is effectivebecause pressures within the pulmonary vein are very close to pressureswithin the left atrium. It will be appreciated by those skilled in theart that visualization markers (not shown) may be provided atappropriate locations on the flexible lead 10 to assist the operator inplacing the device as desired. With the flexible lead 10 in place asshown, the body's own natural healing mechanism may permanently anchorthe flexible lead 10 in place both at the penetration site through theatrial septum 41, and where the flexible lead 10 contacts the interiorsurface of the pulmonary vein 50 in which the tip of the lead 10resides. The pressure transducer 15 might also be placed at locationssuch as the left atrial appendage (not shown in FIG. 9) where thepressure is nearly the same as the left atrium 36, or the leftventricular cavity, where at identifiable phases of the cardiac cyclethe pressure is momentarily nearly the same as that in the left atrium36.

FIG. 11 and FIG. 12 show alternative methods and devices for anchoringthe pressure transducer 15 in a location appropriate for measuringpressures within the left atrium 36. The lead in this embodimentincludes a helical screw 57 for anchoring the lead to the atrial septum41. Similar configurations are used in some leads for pacemakers andthus may be familiar to those skilled in the art.

Referring now specifically to FIG. 11, the guidewire 25 is shownpositioned across the atrial septum 41 between the left atrium 36 andthe right atrium 30. A first lead component 53 is delivered over theguidewire through an appropriate guiding catheter 55 or sheath. Thisfirst lead component 53 includes a helical screw 57 on its exteriorsurface. The helical screw 57 is advanced into the tissue of the atrialseptum 41 by applying torque to the shaft of the first lead component53. The helical screw 57 could also be coupled to a hollow or solidcylindrical mandrel (not shown), or to a spirally wound mandrel (alsonot shown) disposed along substantially the entire length of the firstlead component. When the helical screw 57 has been turned and advancedsufficiently into the atrial septum 41, the guidewire 25 and guidingcatheter may then be withdrawn leaving the first lead component 53anchored securely in place.

iv. Two-component Lead with Optional Second Pressure Transducer

In one embodiment, a second lead component 60 is advanced as shown inFIG. 12 through a central lumen in the first lead component 53. Thefirst and second lead components 53, 60 are sized and configured so thatwhen the second lead component 60 is fully advanced with respect to thefirst lead component 53, a left atrial pressure transducer 62 at the endof the second lead component 60 protrudes by an appropriatepredetermined amount into the left atrium 36. In one embodiment, thesecond lead component 60 is then securely fixed with respect to thefirst lead component 53.

It should be noted that the embodiments depicted in FIG. 11 and FIG. 12includes a second pressure transducer 65 on the exterior of the firstlead component 53 that may be exposed to pressure within the rightatrium 30. This illustrates, in a simplified way, the general principle,in which a pressure transducer is used to measure fluid pressure withinthe left atrium, but in which one or more additional transducers orsensors may also be used to detect a physiologic condition other thanleft atrial pressure. These physiologic conditions may include pressuresin locations other than the left atrium 36, and physical parametersother than pressure.

v. Alternative Anchoring Systems and Methods

FIG. 8 and FIG. 13 through FIG. 16 show embodiments of the flexible lead10, in which folding spring-like fins or anchors deploy to anchor thelead in place in the atrial septum 41. Referring specifically to FIG.13, a first lead component 53 is advanced through a sheath 67, thesheath 67 having been advanced across the atrial septum 41. In thisembodiment, the first lead component 53 includes folding distal anchors68 and proximal anchors 70 that lie folded and are held in place insidethe interior lumen of the sheath 67. When the first lead component 53and sheath 67 are properly positioned, which will generally involve theuse of fluoroscopy or an alternative technique for imaging, the operatormay carefully withdraw the sheath 67 from around the first leadcomponent 53. As the distal and proximal anchors exit the sheath 67,they deploy themselves (as depicted in FIG. 8) on either side of theatrial septum 41, thereby anchoring the first lead component 53 securelyin place. Similar anchors are sometimes used with leads for pacemakersand other medical devices where permanent anchoring is desired, and theoperation of these anchors thus will not be entirely unfamiliar to theknowledgeable reader.

Referring now to FIG. 14, a second lead component 60 is advanced througha central lumen of the first lead component 53 after the guidewire 25(see FIG. 15 and FIG. 16) and sheath 67 are removed. As in the previousembodiment, a left atrial pressure transducer 62 is carried at thedistal end of the second lead component 60. Again, the first and secondlead components 53, 60 are sized and configured with respect to oneanother so that the left atrial pressure transducer 62 protrudes fromthe first lead component 53 an appropriate amount into the left atrium36. In addition, as in the previous embodiment, a second pressuretransducer 65 on the exterior of the first lead component 53 allows forthe measurement and transmittal of pressure within the right atrium 37.

Other anchoring methods may be devised by those skilled in the relevantarts. Moreover, approaches have been described by which the lead ispositioned between the left atrium and an exit site from the patient'ssuperior venous circulation. Alternate lead routes and exit sites mayfind use as well.

vi. Surgical Methods of Device Implantation

As described above, percutaneous transvenous implantation methods areused in accordance with several embodiments of the current invention.One skilled in the art will understand that alternative lead routes andexit sites from the venous system may also be used. One important classof alternative implantation methods consists of surgical implantationthrough the wall of the heart, either directly into the left atriumthrough the left atrial free wall or left atrial appendage, into theleft atrium via a pulmonary vein, into the left atrium through theintra-atrial septum via the right atrial free wall, or directly into apulmonary vein.

In one embodiment, the pressure transducer is implanted in the atrialfree wall or in the wall of the atrial appendage. As described above, inone embodiment, at these locations the pressure sensing surface of thetransducer is exposed to left atrial pressure, and the body of thetransducer extends through the wall of the atrium or atrial appendage. Aflexible lead from the implanted transducer provides signal connectionto a telemetry antenna coil that the surgeon implants near the surfaceof the skin. In another embodiment, this coil may be connected directlyto the implanted pressure transducer on the outside surface of theheart, without need for a flexible lead. In yet another embodiment, theflexible lead provides signal connection to a CRM generator housinglocated near the surface of the skin.

c. Pulmonary Vascular Implant

Vascular stents are implants that are deployed in blood vessels tosupport the size of the vascular channel and maintain adequate bloodflow. A stent may also be used to anchor another type of device in afixed location within the cardiovascular system. U.S. Pat. No.5,967,986, incorporated by reference herein, describes a stent coupledto one or more pressure transducers for the purpose of measuring bloodflow in a vessel. In one embodiment of the current invention, a stent isused to support and anchor the sensor measuring a signal indicative ofleft atrial pressure. As mentioned above, the pressure in the pulmonaryveins is substantially identical to that in the left atrium. Thus, inone embodiment of this invention, the pressure sensor is anchored in apulmonary vein by means of a stent expanded within the vein.

In one embodiment of the current invention, a method and apparatus forcontinuous ambulatory detection, diagnosis and treatment of acutecongestive heart failure is provided. It will be understood that thecurrent invention may be implemented using digital signal processingmethods in which various input signals are sampled and the describedprocedures are performed on a set of samples. Hence, a periodicdetermination of the physiological parameter of interest is within thedefinition of the term continuous. In one embodiment, a percutaneouslyimplantable system comprises a hermetically sealed pressuretransducer/communications module mounted on an unexpanded vascularstent-like member. In one embodiment, the stent-like member is acylindrical vascular stent such as a balloon expandable orself-expanding metallic stent similar to those used to treat vascularstenosis such as atherosclerotic stenosis of a coronary or peripheralartery. The pressure transducer/communications module is mechanicallycoupled to the unexpanded stent and the stent/transducer module ismounted on a delivery catheter constituting a stent/transducer deliverysystem. The stent/transducer delivery system is percutaneously insertedinto a patient's body via the venous or arterial system.

In one embodiment, the delivery system courses over a guide wire thathas been positioned from proximal to distal, starting outside thepatient, percutaneously entering into the venous system and into theright atrium, through the right ventricle and into a branch of thepulmonary artery. The stent/transducer module is then advanced over theguide wire into the selected branch of the pulmonary artery that isapproximately the diameter of the expanded stent/transducer module.

In another embodiment, a standard transseptal catheterization procedureis performed to place a guide wire that courses from proximal to distalstarting outside the patient percutaneously into the venous system intothe right atrium, across the intra-atrial septum, into the left atriumand finally into one of the four pulmonary veins. The stent/transducerdelivery system is then advanced over the guide wire until theunexpanded stent/transducer is positioned in the pulmonary vein that isapproximately the diameter of the expanded stent/transducer module. Thestent is then expanded such that the cylinder described by the stent iscoaxially in contact with the vessel wall confining thetransducer/communications module so that its outer surface contacts thevessel wall.

2. Pressure Transducer

a. Pressure Sensor Locations

In one embodiment of the invention, the apparatus and/or method fortreating cardiovascular disease includes one or more sensors, such aspressure sensors. In one embodiment, the pressure sensor is located inthe atrial septum, the left atrial appendage, one of the pulmonaryveins, or any other location in pressure communication with the leftatrium, for example, but not limited to, the right atrium, the centralveins, or any location as known to those of skill in the art suitablefor measuring a pressure related to the pressure in the pulmonary veins,the pulmonary capillary wedge pressure, the pulmonary artery diastolicpressure, the left ventricular end diastolic pressure, or the rightventricular end diastolic pressure. In one embodiment, the pressuresignal includes a pulmonary vein pressure, a pulmonary capillary wedgepressure, a pulmonary artery diastolic pressure, a left ventricular enddiastolic pressure, a right ventricular end diastolic pressure, rightatrial pressure, or the pressure measured in the intrathoracic space, orthe central veins. In another embodiment, the signal includes algorithmsthat estimate pulmonary artery diastolic pressure from the rightventricular waveform, the right ventricular end diastolic pressure, orthe right atrial pressure.

b. Pressure Sensor Design

In one embodiment, the physiological sensor includes a pressuretransducer. In one embodiment, the pressure transducer is containedwithin a hermetically sealed sensor package, or module. The sensorpackage may be provided in a wide range of sizes and shapes. In oneembodiment, the sensor package is cylindrical, and is between about 1 mmand 5 mm long, and 3 mm in diameter. In another embodiment, the sensorpackage is between about 5 mm and about 15 mm long. In anotherembodiment the package is about 8 mm long, and about 3 mm in diameter.In one embodiment the package is less than about 1 mm in diameter. Inanother embodiment, the package is less than about 10 mm long.Microsensors may also be used. In one embodiment, the package may berectangular, square, spherical, oval, elliptical, or any other shapesuitable for implantation. In one embodiment, the sensor package isrigid, and in another embodiment, the sensor package is flexible.

In one embodiment, the sensor package includes a titanium cylindricalhousing that is closed at one end by titanium foil membrane. In oneembodiment, the foil membrane is between about 0.001 to 0.003 inches,between about 0.003 inches and about 0.005 inches, or less than 0.001inches thick. In another embodiment, the foil membrane is between about25 microns to about 50 microns thick, and about 0.08 to 0.10 inches(about 2.0 to 2.5 mm) in diameter. Foil diaphragms of this type haverelatively low compliance, meaning that they exhibit relatively littlestrain, or displacement, in response to changes in pressure. Forexample, in one embodiment, a 2.5 mm diameter by 50-micron thicktitanium foil diaphragm has a displacement at its center of only about4.3 nanometers per mm Hg pressure change. Higher compliance is adisadvantage for implantable pressure sensors because tissue overgrowthcan limit the relatively larger motion of a high compliance diaphragm,causing errors in the sensed pressure reading.

In one embodiment, resistive strain gauges are bonded to the insidesurface of the foil.

In one embodiment, the titanium cylindrical housing comprises anapplication specific integrated circuit (ASIC or “chip”) or “measurementelectronics.” Measurement electronics are contained within the housing,connected to the strain gauges by fine gold wires. The other end of thehousing is sealed by a ceramic feed-through that is brazed to a titaniumcylinder.

In one embodiment, the pressure of the gas sealed in the cylinder isslightly lower than the lowest external pressure anticipated, so thatthe net force on the foil will be inward under normal conditions ofoperation, forming a concave membrane shape. The advantage ofmaintaining a concave membrane shape throughout the pressure range ofoperation is that it avoids potential pressure measurement artifactsthat are known to sometimes occur when a pressure sensing membranetransitions between a concave and a convex shape, a phenomenon known as“oil-canning.” In one embodiment, oil-canning is avoided by using atransducer diaphragm that has low compliance, with low compliance asdescribed above, and that is nearly flat in the absence of a pressuredifferential. In one embodiment, the diaphragm is about 2.0 to 2.5 mm indiameter and is within about 25 microns of flat in the absence of apressure differential. In another embodiment, the diaphragm thickness ismaximized to maximize flatness and minimize compliance, consistent withthe sufficient compliance to derive a useable transducer signal.

In one embodiment, the pressure sensor includes temperature compensationso that pressure measurements will not be affected by temperaturechange. This also provides the temperature at the site of the sensor. Inone embodiment, temperature compensation or modulation is achieved byusing multiple resistive strain gauges arranged in a Wheatstone bridge,such that the electrical voltage output of the bridge is proportional tothe ratio of two or more resistances, as is well known in the art ofelectrical measurements. By selecting resistive strain gauges withsubstantially identical temperature coefficients, the intrinsic outputof the bridge is made to be temperature independent. However, theoverall response of the pressure transducer may still be temperaturedependent due to other factors, such as the different thermal expansionsof the various components and contents of the device. Another embodimentof temperature compensation utilizes an internal thermometer consistingof, for example, a resistor whose resistance depends upon temperature ina reproducible way, and which is placed in a location isolated from thetransducer diaphragm so that its resistance does not depend on pressurevariations. Prior to implanting the device, calibration data iscollected consisting of the output of the transducer versus pressure asa function of the reading of the internal thermometer. Afterimplantation, the signal from the internal thermometer is used togetherwith the transducer output and the calibration data to determine thetemperature compensated pressure reading. In one embodiment, a band gapvoltage reference is used to create a current proportional to absolutetemperature that is then compared to the temperature-independent voltagereference. Such methods are well-known in the art of CMOS integratedcircuit design.

In one embodiment, the devices described herein are configured similarlyto a cardiac pacemaker, with a hermetically sealed housing implantedunder the patient's skin and a flexible lead with a pressure transducerat its distal end. The housing contains a battery, microprocessor andother electronic components, including a patient signaling device andtranscutaneous telemetry means for transmitting programming informationinto the device and for transmitting physiological data out to anexternal programmer/interrogator.

One skilled in the art will understand that alternative distributions ofthe components may be constructed in accordance with several embodimentsof the present invention. In one alternative, the pressure sensingcircuitry is incorporated into the pressure transducer unit implanted inthe heart, reducing the number of conductors needed in the lead to aslow as two.

In another embodiment, the signal processing, prescription algorithms,and patient signaling components are located in a device external to thepatient's body in communication with the implanted subcutaneous housingvia one of various forms of telemetry well known in the art, such astwo-way radio frequency telemetry.

In another embodiment, the pressure sensor is fabricated by microelectro-mechanical systems (MEMS) techniques, as taught by, for exampleU.S. Pat. No. 6,331,163, herein incorporated by reference.

c. Sensor-Tissue Interaction Issues

In one embodiment, within several weeks after implantation, the entiredevice is covered with new tissue, including fibrous tissue andendothelium. A covering of endothelium is desirable because it preventsthe formation of blood clots that, if formed, could break loose andcause a blocked artery elsewhere in the body, most dangerously in thebrain. A covering of fibrous tissue is also a common component of thebody's healing response to injury and/or foreign bodies. An excessivegrowth of fibrous tissue on the left atrial surface of the pressuresensor may be undesirable because it may interfere with accuratetransmission of fluid pressure in the left atrium to the pressuresensitive diaphragm. In addition, contraction of fibrous tissue overtime may cause progressive changes in the pressure waveform or meanvalue, which could confound interpretation of the data.

i. Low Compliance Sensor Membrane

In one embodiment, the pressure transducer membrane is designed to havevery low compliance. In one embodiment, a low compliance pressuretransducer is fabricated using titanium foil as described above. Inanother embodiment, a low compliance pressure transducer is fibricatedfrom, for example, silicon, using micro electromechanical systems (MEMS)techniques. In yet another embodiment, a coating is provided on the leftatrial surface of the pressure sensor.

ii. Coatings, Polishing, and Drug Eluting Surfaces

In one embodiment, a coating inhibits or minimizes the formation ofundesirable fibrous tissue, while not preventing the beneficial growthof an endothelial covering. Coatings with these properties are wellknown in the art of implanting medical devices, particularlyintravascular stents, into the blood stream. Surface coating materialsinclude, but are not limited to, paralene, PVP, phosphoryl choline,hydrogels, albumen affinity, and PEO.

In one embodiment, at least some areas of the sensor package anddiaphragm are electropolished. Electropolished surfaces are known bythose skilled in the art to reduce the formation of thrombosis prior toendothelialization, which leads to a reduced burden of fibrotic tissueupon healing. All metallic intracoronary stents currently approved forclinical use are electropolished for this purpose.

Release of antiproliferative substances including radiation and certaindrugs are also known to be effective in stenting. Such drugs include,but are not limited to, Sirolimus and related compounds, Taxol and otherpaclitaxel derivatives, steroids, other anti-inflammatory agents such asCDA, antisense RNA, ribozymes, and other cell cycle inhibitors,endothelial promoting agents including estradiol, antiplatelet agentssuch as platelet glycoprotein IIb/IIIa inhibitors (ReoPro),anti-thrombin compounds such as heparin, hirudin, hirulog etc,thrombolytics such as tissue plasminogen activator (tPA). These drugsmay be released from polymeric surface coating or from chemical linkagesto the external metal surface of the device. Alternatively, a pluralityof small indentations or holes can be made in the surfaces of the deviceor its retention anchors that serve as depots for controlled release ofthe above mentioned antiproliferative substances, as described byShanley et al. in U.S. Publication No. 2003/0068355, published Apr. 10,2003, incorporated by reference herein.

d. Pressure Signal Detection

In one embodiment, the implanted portion of the device is comprised of aplurality of up to n physiologic signal detection sensors S described bythe set:

{S₁, S₂, . . . S_(n)}.

In one embodiment, S₁, the first sensor, detects a parameter that isindicative of left atrial pressure or S_(iLAP), thus

{S_(iLAP), S₂, . . . S_(n)}.

Signals indicative of left atrial pressure can be pressure signalsmeasured at a variety of sites and may be detected by a variety ofpressure transducer types. The signals may be obtained from locations inthe cardiovascular system or adjacent to the cardiovascular system knownto be similar to or highly correlated with direct pressure readings fromthe left atrium. Such locations for obtaining pressure signals similarto the left atrium are well known to those skilled in the art, such asCardiologists. Locations for sensing pressure include, but are notlimited to, the left atrium and its contiguous structures, the pulmonaryveins, the pulmonary capillary wedge or occlusion pressure, thepulmonary artery diastolic pressure, and the left ventricular enddiastolic pressures. Other pressures indicative of left atrial pressureinclude differential pressures such as the difference between the leftatria and the right atria, or the difference between the pulmonarycapillary wedge and right atrial pressures, as shown by the correlationin FIG. 17. The individual signals comprising the differential signalcorrelate independently with left atrial pressure.

3. Non-Pressure Sensors

a. Left Atrial Dimension

In one embodiment, the system may include one or more additionalsensors. In one embodiment, a non-pressure sensor is also provided togenerate a signal indicative of pressure in the left atrium. Hemmingsson(U.S. Pat. No. 6,421,565), incorporated by reference herein, describessuch an implantable cardiac monitoring devices as an A-mode ultrasoundprobe which is adapted to be positioned in the right ventricle of aheart, and which emits an ultrasound signal which is reflected from onecardiac segment of the left ventricle of the heart, and the ultrasoundprobe receives the resulting echo signal. The delay between the emissionof the ultrasound signal and the reception of the resulting echo ismeasured, and from this delay a position of the cardiac segment isdetermined. In one embodiment, an A-mode ultrasound probe is deployed inthe right atrium of a heart so that an ultrasound signal is reflectedfrom one or more cardiac segments of the left atrium, either the atrialseptal segment, the lateral wall segment, or both. Increased left atrialpressure is known to cause in increase in the volume of the left atriumby displacing the walls of the left atrium away from each other. Thus,measurement of the positions of one or more left atrial walls provides asignal indicative of left atrial pressure, as described below, that canbe used to guide therapy for CHF.

Kojima (U.S. Pat. No. 4,109,644), incorporated by reference herein,describes another implantable ultrasound transducer that could be usedin the manner described above to determine left atrial dimension andthus derive a signal indicative of left atrial pressure.

In one embodiment, the sensor comprises one pressure sensor, a pressuresensor package, or module, with pressure sensor and electronics, or asensor package containing electronics, a pressure sensor, and at leastone non-pressure sensor. In one embodiment, the at least onenon-pressure sensor provides a signal indicative of: an internalelectrocardiogram; a temperature; a physical dimension; an electricalresistance, such as, but not limited to, a thoracic electricalimpedance; a respiratory tidal volume; a respiratory rate; lungacoustics; oxygen saturation; oxygen partial pressure, including oxygenpartial pressure in the left chamber or the right chamber; or cardiacoutput. In another embodiment of the invention, the non-pressure sensormeasures: left atrial dimension, cross-sectional area, or volume; leftventricular dimension, cross-sectional area or volume; atrial septumposition; velocity, or acceleration. In one embodiment, a non-implantedsensor is provided. In one embodiment, the non-implanted sensorincludes: an arterial pressure cuff, including an automated arterialpressure cuff; and a weight scale. In one embodiment, two sensors areprovided, a first sensor and a second sensor. In one embodiment, thefirst sensor measure a pressure in the heart and the second sensormeasures a non-pressure parameter, including, but not limited to theparameters listed above. In one embodiment, the second sensor is also apressure sensor. In one embodiment, the first sensor is located internalto the patient and the second sensor is located external to the patient.Located “external”, as used herein, shall be given its ordinary meaningand shall also mean located on the patient, in contact with the patient,or located completely independent of the patient.

b. Core Temperature

Other non-pressure physiologic parameters may be used in otherembodiments. Casscells III, et al. (U.S. Pat. No. 6,454,707),incorporated by reference herein, describe a method and apparatus forpredicting mortality in congestive heart failure patients by monitoringbody temperature and determining whether a downward trend in temperaturefits any predetermined criteria. The apparatus described by Casscells etal. determines when death is imminent and generates an alarm. In oneembodiment of the present invention, the trend in body temperature isused daily to adjust the patient's therapy at an earlier point beforeany downward trend in temperature becomes critical. In one embodiment,core body temperature is measured at the atrial septum. In anotherembodiment, core body temperature is measured at the site of ameasurement module located anywhere within the heart, heart chambers,great vessels, or other locations within the thorax known in the medicalarts to maintain a temperature related in a predictable way to core bodytemperature.

4. Signals

a. Left Atrial Pressure Signals

In one embodiment, one of the physiological sensors is a pressuretransducer that is used to generate a signal indicative of pressure inthe left atrial chamber of the patient's heart (the “left atrialpressure,” or LAP). In one embodiment, a LAP versus time signal isprocessed to obtain one or more medically useful parameters. Theseparameters include, but are not limited to, mean LAP, temporallyfiltered LAP (including low-pass, high-pass, or band-pass filtering),heart rate, respiratory variations of LAP, respiration rate, andparameters related to specific features of the LAP waveform such as theso-called a, v, and c waves, and the x, x′, and y descents. All theseparameters are well known to those skilled in the art. Examples of suchfeatures in normal cardiac pressure tracings are illustrated in FIG. 18.Examples of parameters derived from specific LAP waveform featuresinclude the mechanical A-V delay interval, as defined below (as distinctfrom the electrical A-V interval derived from the electrocardiogram);the relative peak pressures of the a and v waves, normal values of whichare given in the table in FIG. 19; and the pressure values at specifictimes in the LAP waveform, as are understood by those skilled in theart.

In one embodiment, signals indicative of left atrial pressure areperiodic signals that repeat with a period the length of which is equalto the period in between heartbeats. Any portion of the signal or asummary statistic of that periodic signal may be indicative of leftatrial pressure and provide diagnostic information about the state ofthe heart. For example, the a, c, v waves and the x, x′, and y descents,described above, correlate with mechanical events such as heart valvesclosing and opening. Any one of these elements can yield usefulinformation about the heart's condition. Each discrete elementrepresents an individual signal indicative of left atrial pressure. Asummary statistic such as the arithmetic mean left atrial pressure alsorepresents a signal indicative of left atrial pressure. One skilled inthe art will appreciate that there are additional discrete elements andsummary statistics that are valuable indicators of left atrial pressure.Advantageously these components of left atrial pressure are relative toeach other and therefore do not have to be compensated for atmosphericpressure and are not subject to offset drift inherent in most pressuretransducers.

In one embodiment, the relative heights and/or shapes of the left atrial“a,” “c,” and “v” waves are monitored to detect and diagnose changes inseverity of cardiovascular disease. This information permitsdifferentiation between worsening symptoms of CHF due to volume overloadversus impaired left ventricular pump function (such as decrease leftventricular compliance, or acute mitral regurgitation), allowing medicaltherapy to be appropriately targeted. For example, pure volume overloadis usually manifest with a progressive elevation of the mean left atrialpressure and generally responds to fluid removal by taking a diureticmedication, natriuretic peptide, or and invasive technique known asultrafiltration of the blood. Decreased left ventricular compliance isthe diagnosis when the “a” wave increases without shortening of theatrioventricular (AV) delay or in the presence of mitral stenosis.Acutely decreased compliance may be indicative of left ventricular (LV)ischemia, while chronically decreased compliance may be indicative of LVwall thickening know as hypertrophy. The former may respond to nitratesor coronary artery interventions, while the latter may respond to betaor calcium antagonist drugs, or chemical septal ablation. Increases inthe “v” wave amplitude and merging with the “c” wave to produce a “cv”wave is usually indicative of acute mitral valve regurgitation. This maybe due to a sudden mechanical failure of the valve or its supportingapparatus, or it may be due to acute ischemia of the supportingpapillary muscles as part of an acute coronary artery syndrome. Suddenmechanical failure requires surgical repair or replacement, whileischemia may require anti-ischemic medications such as nitroglycerin orcoronary artery interventions such as angioplasty or bypass surgery.FIGS. 6A-6C list these and other parameters derivable from cardiacpressure tracings that may be interpreted to facilitate diagnosis ofcardiovascular disease states.

In another embodiment, atrial fibrillation and atrial flutter aredetected by analysis of the LAP waveform. In another embodiment,spectral analysis of the LAP versus time signal is performed.

i. Measurement of Absolute Pressure

In one embodiment, an apparatus for measuring absolute pressure at alocation within the body is provided. In one embodiment, the apparatusincludes a transducer/communications module for making measurements, andcommunicating the measurement to another device, as described above. Thetransducer/communications module can include transducers or sensorssuitable for measuring pressure, as are well known to those of skill inthe art, temperature, or other physiological parameters. In oneembodiment, the transducer/communications module measures an absolutepressure. In another embodiment, the transducer/communications modulemeasures the pressure difference between a location in the body and areference pressure within the implanted transducer/communicationsmodule.

ii. Measurement of Relative Pressure (Gauge Pressure)

In one embodiment, the system contains the necessary components toobtain a signal indicative of pressure relative to atmospheric pressure.An implanted apparatus for measuring absolute pressure at a locationwithin the body is provided as above, which further communicates thisinformation, as either an analog or digital signal, to an externalsignal analyzer/communications device. The external signalanalyzer/communications device further contains a second pressuretransducer configured to measure the atmospheric (barometric) pressure.The analyzer/communications device performs a calculation using theabsolute pressure from the implanted module and the atmospheric pressureto obtain the internal pressure relative to atmospheric pressure, thatis, difference between the absolute pressure at the location within thebody and the absolute barometric pressure outside the body. Thispressure, also known as the gauge pressure, is known to those skilled inthe art to be the most physiologically relevant pressure measure. Theimplanted module may contain an internal power source such as a battery,or it can be powered transcutaneously by induction of radio frequencycurrent in an implanted wire coil connected to the module to charge aninternal power storage device such as a capacitor.

In one embodiment, gauge pressure measurements are performed only whenthe implanted apparatus is queried by the externalanalyzer/communications device, advantageously assuring that theatmospheric pressure at the time and patient's location is available andcorrectly matched with the absolute internal pressure reading. It willbe clear to those skilled in the art that unmatched internal andbarometric pressure readings would render the gauge pressure measurementinaccurate or useless. In this embodiment, internal absolutemeasurements are made only when the external analyzer/communicationsdevice is physically present. In one embodiment, this is accomplished byhaving the external device supply operating power to the implant moduleto make the measurement. In another embodiment, this is accomplished byrequiring a proximity RF link to be present between the external andimplantable modules, either immediately before and/or after and/orduring the measurement.

Other arrangements of pressure transducers will be apparent to oneskilled in the art. The transducer/communications module may containother types of sensing apparatus. In one embodiment, in addition to theimplanted pressure sensor, electrocardiographic and temperature sensorsare provided.

iii. Measurement of Differential Pressure

In another embodiment, an apparatus for measuring differential pressureis provided. In one embodiment, the apparatus includes atransducer/communications module for making measurements, andcommunicating the measurement to another device, such as a processor, orpatient advisory module. The transducer/communications module caninclude transducers or sensors (these terms are used synonymouslyherein), suitable for measuring pressure as are well known to those ofskill in the art, temperature, or other physiological parameters. In oneembodiment, the transducer/communications module measures a differentialpressure that includes the pressure difference between two locationsinside of the body. For example, the transducer/communications modulemeasures the difference between the fluid pressure of the blood in anartery, and the intrathoracic pressure, detected through the artery'swall. In another example, the transducer/communications module measuresthe difference between the fluid pressure in the left atrium and theleft atrium of the heart, detected by a module

In one embodiment, the transducer/communications module includes aplurality of pressure sensing membranes, each with an outer surface andan inner surface. In one embodiment, there are two pressure sensingmembranes in the module so that when the device is implanted, forexample in the atrial septum, one pressure sensing membrane's outersurface is in contact with the blood of the left atrium and the otherpressure sensing membrane's surface is in contact with the blood of theright atrium. The inner surfaces of both pressure-sensing membranes areexposed to the same internal space within the device. Each membrane hasan associated strain gauge, each strain gauge creating a signalindicative of the pressure difference between the outer and the innersurfaces of the respective membrane. Since the two membranes share theinternal space, the pressures on their inner surfaces are equal. Thus,the differential pressure, determined by subtracting the pressure of onetransducer from the other, is proportional to the left atrial pressurein reference to the right atrial pressure. The baseline-offsetcalibration of the differential transducer can be determined by havingthe patient perform a Valsalva maneuver, which is known by those skilledin physiology to equalize the pressure within the chambers of the heart.

In one embodiment, the module contains the necessary components toobtain from the transducers a signal indicative of differentialpressure, and to communicate this information either as an analog ordigital signal, indicative of the severity of a condition, such ascongestive heart failure, to an external signal analyzer/communicationsdevice. The implanted module may contain an internal power source suchas a battery, or it can be powered transcutaneously by induction ofradio frequency current in an implanted wire coil connected to themodule to charge an internal power storage device such as a capacitor.

b. Other Measures Indicative of Left Atrial Pressure

In one embodiment, pulmonary artery diastolic pressure (PADP) isestimated from an analysis of the right ventricular pressure waveform,as taught by Carney in U.S. Pat. No. 5,368,040, incorporated byreference in its entirety herein. In one embodiment, the pressure moduleis placed in the right ventricle. In other embodiments, the pressuremodule is placed in the right atrium or a pulmonary artery. It is knownto those skilled in the art that under certain circumstances, PADPapproximates the pulmonary capillary wedge pressure (PCWP), which is aclinically useful measure of mean left atrial pressure. In this case,the right ventricular pressure waveform provides a signal indicative ofleft atrial pressure.

In several embodiments, non-pressure physiologic signals are used toindicate left atrial pressure. In most cases, these non-pressurephysiologic signals correlate to left atrial pressure throughstraightforward mathematical relationships. For example, for periodicsignals of left atrial pressure and volume, a periodic pressure-volumerelationship may be used. One well-known example of a pressure-volumerelationship occurs during atrial diastole, when the ratio ΔV/ΔP, knownas the diastolic compliance, is generally stable. Thus, a given leftatrial volume, cross-sectional area or any dimension indicative of thatvolume is also a signal indicative of left atrial pressure, and a sensorcapable of measuring a left atrial dimension or area may be used todetermine left atrial pressure. Thus, in one embodiment of theinvention, one or more physiological sensors are provided to directly orindirectly sense one or more of the following physiological parameters:left atrial dimension, cross-sectional area, and/or volume; leftventricular dimension, cross-sectional area or volume; atrial septumposition; heart chamber wall velocity, and/or acceleration.

Examples of sensors capable of measuring such dimensions or areasinclude, but are not limited to an intracardiac ultrasonic imagingsystem operating in M-mode, 2-dimensional, or 3-dimensional modes, aswell as paired ultrasonic crystals. It is well known in the art thatheart chamber dimensions or cross-sectional areas may be measured andvolumes estimated by the use of ultrasound, as described, for example,by Kojima (U.S. Pat. No. 4,109,644) and by Hemmingsson (U.S. Pat. No.6,421,565), both incorporated by reference herein. Such ultrasonicsystems may have additional diagnostic value in that Doppler analysiscan detect changes in atrial flow patterns due, for example, to mitralregurgitation.

It is also known in the art that electrical impedance changes may beindicative of changes in heart chamber dimensions. An example of aphysiological sensor suitable for use in one embodiment of the currentinvention is described by Alt (U.S. Pat. No. 5,003,976), incorporated byreference herein. Alt describes how analyzing the impedance between twointracardiac electrodes may be used to determine changes in cardiacchamber volumes, which under certain circumstances as described aboveare indicative of changes in chamber pressures, and thus may be used todetect worsening heart failure and guide therapy according to thepresent invention.

In accordance with the above description, an embodiment of the presentinvention comprises a physiologic signal detection sensors set which maybe alternately described as:

{S_(iLAV), S₂, . . . S_(n)}, where S_(iLAV) is a sensor indicative ofleft atrial volume;

{S_(iLAA), S₂, . . . S_(n)}, where S_(iLAA) is a sensor indicative ofleft atrial cross-sectional area; or

{S_(iLAD), S₂, . . . S_(n)}, where S_(iLAD) is a sensor indicative ofleft atrial dimension;

where the first sensor in all sets detects a signal that is indicativeof left atrial pressure. Additional sensors in the implanted portion ofthe device may include detectors for any other physiologic signal. Forexample:

{S_(iLAP), S_(iLAD), S_(iECG), S_(iCT), S_(iO2), . . . S_(n)},

where sensors denoted by subscripts iECG, iCT, iO₂ are detectors orsignals indicative of the electrogram, core temperature, and oxygensaturation, respectively. One skilled in the art will appreciate thatthere are numerous sensor configurations and sensor types that may beused in accordance with various embodiment of the present invention.

In one embodiment of the invention, multiple physiologic sensors arecontained in a single package. In another embodiment, a plurality ofpackages is spatially distributed. Some of the packaging may place aparticular sensor outside of the body. For example, in one embodiment,signal detection sensor packages P₁, P₂, and P₃ may be locatedinternally or external to the body and consist of the following sets:

P₁={S_(iLAP), S_(iCT)}, located in the intra-atrial septum;

P₂={S_(iECG)}, located in the superior vena cava; and

P₃={S_(iABP)}, where iABP is a signal indicative of arterial bloodpressure.

One skilled in the art will appreciate that several embodiments of thecurrent invention include the detection of various signals indicative ofleft atrial pressure. Such signals include, but are not limited to: a,c, v, x, x′, and y of LAP, mean LAP, the respiratory portion of LAP, thetotal cardiac portion of LAP, and filtered LAP between frequencies. Inseveral embodiments, non-LAP signals are used. These non-LAP signalsinclude, but are not limited to, the detection of a and b left atrialvolume, left ventricular volume, atrial fibrillation, atrial flutter,respiratory tidal volume, respiratory rate, weight change, bloodpressure or change in blood pressure, core temperature, oxygensaturation, oxygen partial pressure, cardiac output, LA to RAtemperature differential, lung acoustic signal, and EEG.

One skilled in the art will understand that numerous configurations ofsensors and sensor packaging and locations may be used in accordancewith various embodiments of the current invention.

c. Other Blood Pressure Signals

In another embodiment, one or more physiological sensors measure centralvenous blood pressure.

In one embodiment of the invention, one or more of the physiologicalsensors measure peripheral arterial blood pressure. Analysis ofperipheral artery blood pressure to obtain a parameter indicative ofcongestive heart failure status has been described, by Finkelstein (U.S.Pat. No. 4,899,758), incorporated by reference herein. In one suchembodiment, the peripheral artery blood pressure sensor may be a cuffsphygmomanometer, and the patient's systolic and diastolic bloodpressures are entered into the signal processing apparatus by the user.In a further embodiment, the blood pressures may be sent by directsignal communication to the signal processor.

d. Other Physiological Parameters

In one embodiment, the internal electrocardiogram (known as the IEGM) issensed at one or more locations. In a further embodiment, the IEGM isprocessed to obtain one or more medically useful parameters. Theseparameters include, but are not limited to, heart rate, the timing ofatrial and ventricular depolarization, the time interval between atrialand ventricular depolarization (known in the art as the A-V interval),the duration of ventricular depolarization (known in the art as the Q-Tinterval), ST segment changes to detect acute ischemia, and spectralanalysis to detect t-wave alternans (a known harbinger of lifethreatening arrhythmias), all of which are familiar to those skilled inthe art.

In one embodiment, one of the physiological sensors is a thermometermeasuring core body temperature, as described above.

In one embodiment of the present invention, Doppler ultrasound providesa signal that is proportional to the relative velocity of the ultrasoundprobe and a structure, such as a heart chamber wall, producing anultrasound echo. A velocity signal can be differentiated to obtain anacceleration, as is well known to those skilled in the art. Conversely,implantable accelerometers are sensors known in the art that provide asignal that is proportional to the acceleration of the implanted sensor.An acceleration signal can be integrated to obtain a velocity plus anarbitrary constant velocity. Because it is known that the averagevelocity of any structure in the body, relative to the body, isnecessarily zero, the arbitrary constant velocity is determined, and therelative velocity signal can be uniquely recovered from the accelerationsignal. Thus, velocity and acceleration measurements of structures inthe heart are essentially equivalent, the one being derivable from theother. As is well known in the art, a velocity signal may be integratedto obtain a position or displacement signal plus an arbitrary constantdisplacement. Thus, the motion and displacement of a structure in theheart, or the range of variation of the dimension of a chamber of theheart, may be recovered from the velocity or acceleration signal of thestructure or of the chamber walls, respectively.

Vallana and Garberoclio (U.S. Pat. No. 5,454,838, incorporated byreference herein) teach that components of the velocity or accelerationsignal are indicative of aspects of cardiac activity, such as opening ofthe mitral valve, closure of the mitral valve, opening of the aorticvalve, closure of the aortic valve, an amount of ventricular ejection,rapid ventricular filling, delayed ventricular filling during atrialsystole, and cardiac flow rate. As these aspects of cardiac activity maybe indicative of changes in the patient's condition, and may beresponsive to changes in the patient's prescription, they are within thescope of parameters contemplated to be used with embodiments of thepresent invention.

In another embodiment of the present invention, a physiological sensormeasures respiratory tidal volume, respiratory rate, lung acousticsignal, and/or thoracic electrical impedance.

In one embodiment of the invention, one of the physiological sensorsmeasures total body weight. In one embodiment, the sensor is a scale. Inanother embodiment, the patient's weight is entered into the signalprocessing apparatus by the user. In another embodiment, the weightsensor is a scale that communicates a signal indicative of the patient'sweight to the signal processing apparatus without requiring a user toenter the value. Lloyd et al. (U.S. Pat. No. 6,080,106), incorporated byreference herein, describe a digital scale suitable for use in oneembodiment of this invention.

In yet another embodiment of the invention, one or more sensors measure:oxygen saturation; oxygen partial pressure in the left, right, both leftand right-sided cardiac chambers, or adjacent great blood vessels; orcardiac output.

5. Signal Processing Apparatus

In one embodiment, the signal processing apparatus of the presentinvention receives signals from the one or more sensors, and processesthem together with stored parameters relevant to the patient's medicalmanagement. In one embodiment, the result of this processing is a signalindicative of the appropriate therapeutic treatment or course of actionthe patient or an immediate personal care giver can take to manage orcorrect, as much as possible, the patient's condition. In oneembodiment, the signal processing apparatus is located outside thepatient's body. In one embodiment, signals from one or more permanentlyimplanted physiological sensors are received by the external signalprocessing apparatus by wireless telemetry. In one embodiment, certainsignal processing is performed within the one or more individual sensordevices prior to the signal being sent to the signal processingapparatus. In one embodiment one signal received by the signalprocessing apparatus is the LAP versus time waveform sampled at over 20Hz for a duration of several respiratory cycles (for example, but notlimited to, 10 to 30 seconds). In one embodiment, the signal processingapparatus also receives a signal from a temperature sensor located atsubstantially the same position as the LAP sensor and uses thistemperature to apply a temperature compensation correction to the LAPsignal using calibration data stored in the signal processing apparatus.In one embodiment, the processor also receives ambient temperature andatmospheric pressure, performs temperature compensation, and subtractsthe atmospheric pressure from the LAP to obtain the relative or “gauge”LAP. In one embodiment, the signal processing apparatus then computesthe mean LAP from the relative LAP versus time waveform. In oneembodiment the signal processing apparatus then compares the mean LAPwith patient-specific treatment ranges for mean LAP that have beenprogrammed into the signal processing apparatus by the patient'sphysician. In one embodiment, for each patient-specific programmedtreatment range the patient's physician stores in the signal processingapparatus an indication of the appropriate therapeutic treatment oraction the patient should take to manage or correct, as much aspossible, the patient's condition. A signal indicative of thephysician-prescribed therapeutic action corresponding to thepatient-specific range into which the measured physiologic parameterfalls is then sent to a patient signaling device.

In another embodiment of the invention, the signal processing apparatusis essentially permanently implanted within the body, in either the sameor a different location as the one or more physiological sensors. In oneembodiment, the sensors may be in signal communication with the signalprocessing apparatus by means of one or more connective leads that maycarry electrical, optical, hydraulic, ultrasonic or other forms ofsignaling energy. The conductive lead(s) may vary in length up to andexceeding about 100 cm. In another embodiment, the sensors may be inwireless communication with the signal processing apparatus. The leadcan be coupled to an antenna for wireless transmission or to additionalimplanted signal processing or storage apparatus.

6. Interpretation of Signals

In one embodiment of the present invention, patients are diagnosed basedupon the interpretation of signals generated by one or more sensors. Forexample, a signal indicating low mean right atrial pressure may suggesthypovolemia or improper zeroing of the transducer. FIGS. 6A-6C provideother examples by which signals may be interpreted to facilitatediagnosis, prevention and treatment of cardiovascular disease accordingto various embodiments of the present invention.

One skilled in the art will understand that other interpretations may beused in accordance with various embodiments of the current invention.Further, one skilled in the art will understand that normal ranges ofthe various physiologic parameters measured in several embodiments ofthe current invention can be found in any cardiology textbook orreference book. Additionally, it may be useful to compare patientparameters within the same patient by ascertaining initial baselinevalues and comparing these baseline numbers to values generated at somelater desired time. This may be particularly useful in determiningprogression of disease and response to treatment.

In several embodiments, sensors in addition to the left atrial pressuresensor are used. Additional sensors provide further refined diagnosticmodes capable of distinguishing between different potential causes ofworsening cardiovascular illness, and then of signaling an appropriatetherapeutic treatment depending upon the particular cause for anyparticular occurrence.

For example, increased left atrial pressure is commonly caused byimproper administration of medication, patient non-compliance, ordietary indiscretion, e.g., salt binging. These causes will be generallywell-handled by changes in the patient's drug regimen like thosedescribed above. However, there are other causes of increased leftatrial pressure that are less common, but by no means rare, and whichrequire different therapies for adequate treatment. For example, onesuch potential cause is cardiac arrhythmia, and especially atrialfibrillation with a rapid ventricular response. Other arrhythmias maycontribute as well to worsening heart failure. A system including an ECGelectrode in addition to the left atrial pressure sensor would allow thesystem to diagnose arrhythmias and determine whether the arrhythmiapreceded or came after the increase in left atrial pressure. Dependingon the unit's programming, as specified by the patient's physician,specific therapies could be signaled tailored to treat the specificcauses and conditions associated with particular adverse events.

In another example of the usefulness of additional physiological signalsis to distinguish between pulmonary congestion caused by worsening CHFand that caused by a respiratory infection. In a further embodiment,core body temperature is used together with left atrial pressure toallow the early detection of fever associated with infection. It is wellknown that core body temperature often becomes elevated hours to daysprior to symptomatic fever associated with infection-related pulmonarycongestion. In one embodiment, increased core temperature in thepresence of stable left atrial pressure would trigger a message to thepatient not to increase the dosage of oral diuretic despite symptoms ofincreasing congestion, and to consult with the physician.

7. Patient Signaling Devices

In one embodiment, the signal processing apparatus and the patientsignaling device are permanently implanted, and the patient is signaledusing at least two distinguishable stimuli, such as distinguishablesequences of vibrations, acoustic signals, or midel electrical shocks,perceptible by the patient.

According to one embodiment of the invention, one or more physiologicalsensors is implanted within the body, the signal processing apparatusand the patient signaling device are located outside the body, and thesignal indicative of a physiological parameter is communicated bywireless telemetry through the patient's skin. In one embodiment, anexternal telemetry system is combined with the signal processingapparatus and the patient signaling device. In one embodiment, ahand-held personal data assistant (PDA), such as the PALM PILOT™ (PalmComputing, Inc.) and/or HANDSPRING VISOR® (Handspring, Inc.), is usedfor the signal processing and patient signaling apparatus. In oneembodiment, patient signaling is accomplished using sound, text, and/orimages.

B. Combination with Other Devices

It will be clear to those skilled in the art that many patients whowould benefit from several embodiments of the present invention wouldalso benefit from an implantable CRM apparatus such as a cardiacpacemaker. In one embodiment, the present invention is combined with animplantable CRM apparatus generator. In one embodiment, the flexiblelead on which the physiological sensor is disposed also serves as thesensing or pacing lead of an implantable rhythm management apparatus. Inthis case, conductors within the lead provide for EKG sensing, poweringof the physiological sensor, data communication for the physiologicalsensor, and pacing stimulus.

In another embodiment, the present invention is functionally integratedwith another implantable device, such as, for example, a pacemaker or adefibrillator. In one embodiment of this invention, one or moreparameters indicative of a physiological condition produced by thepresent invention are used by the integrated device to control itstherapeutic function, as described below.

In yet another embodiment, the sensor and lead of the Stand-Alone devicemay be connected without modification either to a subcutaneous coilantenna as described above, or to a combination CRM generator housingcontaining a battery power supply and other components as describedbelow. In one embodiment the device may be upgraded after permanentimplantation by replacing the coil antenna assembly with an implantableCRM apparatus.

1. Combination with Cardiac Rhythm Management (CRM) Apparatus

Many patients who might benefit from several embodiments of the presentinvention described above would also be likely to benefit from animplantable CRM apparatus for therapy of brady- or tachy-arrhythmia inthe setting of CHF. Examples of such CRM devices include single ormultichamber cardiac pacemakers; automatic implanted cardiacdefibrillators; combined pacemaker/defibrillators; biventricularpacemakers; and three-chamber pacemakers, all well known to thoseskilled in the art. In these patients, it would be beneficial to combineseveral embodiments of the present invention with such a CRM device.This combination would have the advantage that certain components ofboth systems could be shared, reducing cost, simplifying implantation,minimizing the number of implanted devices or leads. As described indetail below, in some embodiments a combination with a CRM apparatusincludes adding pacing and/or defibrillation to the therapeutic actionsincluded in the dynamic prescription of several embodiments of thepresent invention.

In one embodiment, a flexible lead serves also as an atrial septalpacing lea. It will be recognized by those skilled in the art, such ascardiologists, that pacing the atrial spectrum provides certainadvantages for patients with congestive heart failure. These advantagesmay include more direct control over left atrial/left ventricularsynchrony, inhibition of atrial fibrillation, and it requires one lesslead to be inserted in patients that are in need of a rhythm managementdevice that includes atrial pacing and a hemodynamic monitoring/therapydevice, etc.

It will also be known to those skilled in the art that pacingmultichamber sites in appropriate sequence in addition to the atria,such as the right ventricle and the lateral wall of the left ventriclein combination, or the lateral wall of the left ventricle alone, hasspecific advantages for some patients with congestive heart failure.FIG. 20 illustrates one embodiment of the present invention in which asensor package 15 at the end of flexible lead 10 is implanted across theatrial septum 41 of a patient's heart 33. The sensor package 15 measuresthe left atrial pressure and also serves as the atrial septal pacingelectrode 215 of a CRM device, which may be located within an implantedhousing 7. A second flexible lead 160 is placed via the right atrium 30into the right ventricle 37. Each lead is shown with an indifferentelectrode 14 proximal to its respective distal electrode 215, althoughthose skilled in the art will recognize one of these could beeliminated. The housing 7 contains the CRM device (not shown), which inone embodiment includes a battery and electrical circuitry for pacingthe heart 33, and components of a physiological monitoring system. Itwill be clear to the skilled artisan that a variety of configurationsmay be used to combine the CRM and physiological monitoring functions ofsuch a combined device, examples of which are described below.

In one embodiment, the housing 7 includes a coil antenna 161 forcommunicating the one or more physiological signals from sensor package15 to an external patient advisory module 6. In one embodiment, theexternal patient advisory module 6 includes a telemetry module 164 andantenna 162, a barometer 165 for measuring atmospheric pressure, and asignal processing/patient signaling device 166, such as described abovewith reference to FIG. 5.

In one embodiment, components are housed within the implantable housingof an implantable CRM apparatus, including but not limited to the powersource, signal processing apparatus, telemetry apparatus, or patientalarm. Alternatively, in another embodiment, components of a CRM may beshared with other implantable devices, such as the apparatus fortreating congestive heart failure described in greater above. Componentsthat may be shared include, but are not limited to, a power source,telemetry module, data memory, etc. For example, the flexiblephysiological sensing lead of any of the apparatus for treatingcongestive heart failure described above may be use as a pacing lead ofa CRM. In other embodiments, separate pacemaker and sensing leads areprovided.

In one embodiment of the present invention, components of the apparatusfor treating congestive heart failure are shared with the components ofa CRM apparatus in such a way that, while sharing components, the twosystems function essentially independently. In one embodiment, theimplantable CRM apparatus generator has a housing that also serves asthe housing for at least some components of the apparatus described ingreater detail above. In a further embodiment, the power supply of theCRM apparatus, typically comprising a long lifetime battery and powermanagement circuitry, also supplies power for one or more components ofthe apparatus for treating congestive heart failure. In yet anotherembodiment, the flexible lead or leads connecting the sensors of theapparatus of FIG. 1, FIG. 2, and FIG. 4, to a shared housing/generatorare also coupled to sensing and/or pacing electrodes of the CRMapparatus.

In one embodiment, one or more separate leads coupled to thephysiological sensor described above, such as a pressure transducer, isalso coupled to the CRM apparatus. In this embodiment, the CRM apparatusshares its generator housing with components of the implantable heartmonitor apparatus described above, but the CRM apparatus leads areseparate from the physiological sensor leads. In another embodiment, thepressure sensing lead may be combined with a pacing lead, as describedfor example by Pohndorf (U.S. Pat. No. 4,967,755) or Lubin (U.S. Pat.No. 5,324,326), herein incorporated by reference.

a. Integration of Sensor and Pacing Lead

In one embodiment of the present invention, a system and method isprovided for combining a CRM apparatus, implantable heart monitor, andpatient communication device. The system provides the followingfunctionality via a single pacing/sensing lead which in one embodimentincludes only two conductors: (1) provides power to the physiologicalmeasurement module(s); (2) provides signaling for atrial pacing andsensing; (3) provides for programming of the physiological sensorpackage(s); and (4) provides measurement data from the physiologicalsensor package(s) to the monitor/defibrillator housing for immediate ordelayed use by the patient, doctor or other caregiver via the patientsignaling module. Additional pacing and/or sensing leads may be added.

In one embodiment, an external telemetry device (such as described abovewith reference to FIG. 4 and FIG. 5) is used to communicate with andquery a CRM/heart monitor system. The external device analyzes the datawith respect to the doctor's prescription, and then indicates to thepatient which and what dose of medications or other actions he or sheshould take. In one embodiment, the data is also provided to the logicwithin the CRM system for improving pacing or defibrillation therapy.

For example, in one embodiment, the pressure waveform from the leftatrial chamber contains information pertinent to adjustingatrioventricular dual chamber or atrio-biventricular triple chamberpacing for optimizing the synchrony between left atrial and leftventricular mechanical contraction. FIG. 21 shows why it is difficultfor pacemakers to automatically control the optimal delay between theleft atrium (LA) and left ventricle (LV). The electricalatrioventricular delay (AV delay), which a conventional CRM system cansense, may be substantially different that the mechanical AV delay,which the conventional CRM cannot sense, but which is the relevantinterval for optimizing cardiac function. The relationship between theelectrical AV delay and the mechanical AV delay is dependent on several,difficult to measure variables, including intra-atrial conduction time,sub-AV node/HIS bundle conduction delays, volume/pressure preloading ofthe atria and ventricles and ventricular contractility, among otherthings, as is known to cardiologists and electrophysiologists. Themechanical AV delay is clinically important because if the delay is toolong, usually greater than about 250 msec, then atrial contraction doesnot have an effective pressure boosting/volume priming effect on theleft ventricle, thus adversely effecting LV contractility, strokevolume, and cardiac output. If the mechanical AV delay is too short,usually less than about 120 msec, atrial contraction occurs against aclosed or closing mitral valve, again adversely affecting atrialemptying, and pressure/volume boosting of the LV pump. Both a too longand a too short LA-LV mechanical delay can potentially worsen heartfailure by further raising the LA pressure. These conditions arepotentially extractable from an LA pressure tracing in the followingways. Too long an LA-LV mechanical delay will manifest as an increase inthe amplitude of the LA pressure “v” wave relative to the “a” wave andan exaggeration of the “x” descent. Too short an LA-LV mechanical delaywill manifest as an increase in the LA pressure “a” wave relative to the“v” wave and a reduction in the “x” descent. As illustrated in FIG. 21,the actual mechanical LA-LV delay can be directly measured from the LApressure waveform as the interval from the onset of LA contractionrepresent by the LA pressure “a” wave, to mitral valve closurerepresented by the “c” wave. In one embodiment, the measured mechanicalAV delay is used to adjust the electrical AV delay by a feedback controlsystem or an algorithm to achieve a preset ideal AV delay, oralternatively by minimizing LA mean pressure.

There are other features in the LA pressure waveform that can be used tomodify pacing parameters such as backup atrial pacing rate andrate-responsive algorithms that will be apparent to one skilled in theart. For example, to increase cardiac output, and potentially lower theleft atrial pressure, the resting heart rate may be raised from thetypical backup atrial pacing rate in the range of 60 to 70 beats perminute when the patient is in compensated heart failure (mean LAP<16-20mm Hg), to a faster backup atrial rate when the patient is decompensatedwith an elevation of LAP. Similarly, the mean left atrial pressure canbe used to modify rate response algorithms, normally based on activity,minute ventilation, or other physiologic parameters, so that the rateresponse is also specific to the state of congestive heart failure.

In another embodiment, the signal processor, dynamic prescription, andpatient signaling device are completely contained within the implantedCRM apparatus housing. Several methods of patient signaling from animplanted device are well known in the art, including the use of mildelectrical stimulation (e.g., U.S. Pat. Nos. 4,140,131, 4,619,653 and5,076,272), or audible sounds (e.g., U.S. Pat. Nos. 4,345,603 and4,488,555), including intelligible speech (e.g., U.S. Pat. No.6,247,474), all herein incorporated by reference.

In another embodiment, the measurement of pressure or otherphysiological parameters may be multiplexed with the pacing signal (asdescribed in greater detail below) so that pressure sensing andtelemetry would occur between pacing signals, for example as taught byBarcel (U.S. Pat. No. 5,275,171) or Weijand et al. (U.S. Pat. No.5,843,135), both incorporated by reference herein.

In one embodiment, pressure sensor electronics are integrated within aminiature hermetically sealed sensor package implanted in the heart,minimizing the number of conductors required in the lead between thesensor and the CRM apparatus generator housing. In this embodiment, thepressure sensor lead may also be used for pacing, with the sensorpackage, or portion thereof, used to include one of the electrodes ofthe CRM apparatus. In addition, in one embodiment, some of the pacingelectronics are integrated within the sensor package that is implantedwithin the heart. This has the advantage that the lead conductors areisolated from the pacing electrode, providing immunity from inducedcurrents when, for example, the patient is placed in the rapidlychanging strong magnetic fields of a magnetic resonance imaging machine.

In clinical use, conventional cardiac pacemakers use analog voltages onthe lead between the pacemaker generator and the heart for pacing,sensing and physiological measurements. As such, the sensing signals inparticular are subject to noise due to muscular activity, radiofrequency (RF) interference, and potential cross-talk betweenphysiological and electrical sensing signals. Lead conductors carryinganalog signals act as antennas for RF noise and for induced voltages dueto RF energy used in magnetic resonance imaging (MRI) scanners. RF noiseon a sense conductor may cause erroneous pacing, even with sophisticatedfiltering algorithms that are commonly used in pacemaker sensingsystems. Voltages induced by RF and changing magnetic fields are aprimary reason why MRI scanning is contraindicated for patients withimplantable cardiac pacemakers.

In one embodiment, a pacemaker is provided in which the electronics forproducing the pacing pulse output and for sensing the ECG are integratedwithin a sensor package at the site of the pacing electrode, which isgenerally implanted within the heart. This allows the lead conductors tobe substantially isolated from the pacing electrode, thereby providingincreased immunity from induced currents when, for example, the patientis placed in the rapidly changing, strong magnetic fields of a magneticresonance imaging machine. The lead may incorporate one or more sensorswithout requiring additional lead conductors.

In one embodiment, the electronics in the proximal housing, for example,a housing implanted near the shoulder, operate at lower voltage thanvoltages required for pacing, and as a result are fabricated usingsmaller feature size CMOS technology. This allows for a smaller packageand lower power consumption. The distal pacemaker components, forexample, those located in the heart, are fabricated using larger featuresize CMOS technology to handle the higher pacing voltage.

In one embodiment, the system allows sensing signals to be processedwithin the heart, thereby eliminating the risk of picking up noise withlead conductors. Separate sensing and pacing electrodes may be provided,with no additional lead conductors. This allows the sensing and pacingelectrodes to be individually optimized. Pacing electrodes are optimallysmall in area to minimize required voltage for pacing, while sensingelectrodes are optimally of large area to minimize impedance.

Referring now to FIG. 22 and FIG. 23, two embodiments of a sensorpackage 200 are shown in which separate electrodes for sensing 202 andpacing 204 are included. In the embodiment of FIG. 22, the sensingelectrode 202 is located at the proximal portion or segment 208 of thesensor package 200, while the pacing electrode 204 is located at thepackage distal portion or segment 210. The sensing and pacing electrodes202, 204 are electrically separated by an insulating segment or ring206. In one embodiment the insulating ring 206 is a cylindrical ceramicsegment to which metallic proximal and distal segments 208, 210 of thesensor package 200 are hermetically fastened. Hermetic fastening may beachieved by using methods that are well known to those skilled in theart, such as, for example, braising.

In one embodiment, the surface area of the pacing electrode 204 isreduced by coating selected areas of the metallic distal segment 210with an insulating material. In one embodiment, the insulating materialis a tenacious thin coating such as, for example, parylene. One or moreselected small areas may be masked off prior to coating to provide forone or more electrically conducting pacing electrodes 204. Referring nowto FIG. 23, in one embodiment, the pacing electrode 204 includes anannular region 222. In another embodiment, the pacing electrodes 204include areas on the distal anchor members 214 such that the pacingcurrent is applied preferentially to the left atrial wall of the septum.In one embodiment, the pacing electrodes 204 include metallic electrodesfastened to tips of one or more of the distal anchor members 214. In oneembodiment, the metallic tip electrodes are made of tantalum, which hasthe desirable property that it can be made as a porous, high surfacearea material. It will be familiar to the skilled artisan that suchmaterials reduce contact impedance with tissue. Tantalum has theadditional property of high x-ray density, which allows the anchor tipsto be visualized under fluoroscopy for verifying the positioning anddeployment of the anchor 214.

Referring now to FIG. 23, in another embodiment, two insulating ceramicsegments 216, 218 are provided, which divide the sensor package housing200 into distal, middle, and proximal metallic segments 220, 222, and224. In one embodiment, the distal and proximal metal segments 220, 224are substantially uncoated and serve as a sensing electrode 202, whilethe middle metallic segment 222 includes the pacing electrode 204. In afurther embodiment, portions of the middle segment 204 are coated with amaterial such as, for example, parylene, to produce one or more smallerarea pacing electrodes.

In one embodiment, the pacing and sensing electrodes 202, 204 of FIG. 22and FIG. 23 are electrically coupled to pacing electronics locatedwithin the sensor package 200. In another embodiment, the sensor packagepacing electronics are configured to detect a specific electrical eventwithin the heart, such as the p-wave of the internal electrogram, as iswell known to those skilled in the art of electrophysiology, cardiologyand cardiac pacing. In one embodiment, the sensor package pacingelectronics are further configured to send a digital signal indicating asensed event, such as detection of the p-wave, to the pacing electronicsin the proximal housing, as described further below.

In one embodiment of the present invention, a defibrillator and animplantable, heart monitor (such as described above with reference toFIG. 1 through FIG. 5) are combined to provide the followingfunctionality via an essentially standard pacing/defibrillator lead withonly two conductors: (1) provide power to a physiologically optimizeddosimeter (POD) measurement module(s); (2) provide signaling for atrialand/or ventricular pacing and sensing, (3) provide for atrial and/orventricular defibrillation through a third lead attached to adefibrillation electrode; (4) provide for programming of thephysiological sensor package; and (5) provide measurement data from thephysiological sensor package(s) to the monitor/defibrillator housing forstorage and recovery by, e.g., a doctor or the patient via the patientsignaling module.

In one embodiment, digital signaling is used to provide for power,two-way data communication, and pacing over a two-wire lead. In oneembodiment, digital signaling consists of dividing a “frame” of adefined duration into a number of distinct sub-frame intervals, eachwith a defined function, as shown in the pulse timing diagram in FIG.24. In one interval, a power pulse may be provided to charge the powersupply of the sensor/pacing module. In one embodiment, the power pulseis provided during the first interval of every frame, so that the powerpulse defines the end of one frame and the beginning of the next frame.In one embodiment, power pulses are generated at a precisely timedfrequency within the generator module and this timing is used within thesensor/pacing module(s) to adjust an internal RC or current source clockfor better synchronization between the distal sensor/pacing module andthe generator module at the proximal end of the lead. Between one powerpulse interval and the next, other intervals may be defined as neededfor the transmission of data and signals over the lead. In oneembodiment, the amplitude or magnitude of the power pulse is the same asthe amplitude or magnitude of the data pulses, such as shown in FIG. 24.However, in other embodiments, the amplitude or magnitude of the powerpulse is greater than, or less than the amplitude or magnitude of thedata pulses. In one embodiment, the amplitude of the power pulse doesnot vary between pulses, and in another embodiment, the amplitude of thepower pulse varies between pulses, or within pulses.

In the embodiment described in FIG. 24, the next two intervals areprovided for signaling from the CRM module to the sensor/pacingmodule(s). In one embodiment, these two intervals are called the“download interval.” The first interval is asserted by the CRM module tocommand that a pacing stimulation pulse be applied (e.g., A-pulseTrigger). The second interval is asserted by the CRM module to indicatethat commands producing a change in the mode of operation of thesensor/pacing module are to follow (e.g., Programming Bit set).Following the download interval, an “upload interval” may be providedfor communication of information from the sensor/pacing module back tothe generator module. As shown in FIG. 24, this information may includea bit that, if asserted, indicates an atrial and/or ventricular sensedevent, and/or measurement data, and/or status information about thecurrent mode of operation of the sensor/pacing module.

In one embodiment, the type of data following the A-sense uploadinterval may be either upload or download data depending, for example,on whether a programming or pacing command had been asserted. In theembodiment of FIG. 24, if neither of the two download bits has beenasserted in the current or the previous frame, the time intervalsfollowing the A-sense interval are used by the sensor/pacing module toupload measured data, such as pressure, temperature and electrogram(IEGM) waveform data. In order to conserve power, the pressure,temperature and IEGM data could be measured and output at a low dutycycle. If the Programming Bit is asserted in the current frame, thesensor/pacing module is set to listen for programming command bits sentby the CRM module. If either the A-pulse trigger or the Programming Bitwas set in the previous frame, the sensor/pacer module provides statusinformation indicating whether the command was successful.

In one embodiment, the download and upload intervals are subdivided intodata words, each containing a predefined number of bits, so thatmultiple pieces of information are communicated. For example, thedownload interval may consist of a pacing command pulse followed by oneor more programming bits. The upload interval may consist of a sensingbit (set if P- or R-wave of internal electrocardiogram is sensed by themeasurement module), followed by a predetermined number of bits ofpressure data, followed by a second predetermined number of bits oftemperature data. All signals, including pressure, IEGM, andtemperature, may be “alternated” in some fashion rather than beingincluded in any single frame, to allow for shorter frames and thereforemore frequent power supply support and synchronization. It will be clearto one skilled in the art that data from additional sensors may beappended in the same way. In one embodiment, additional checksum bit(s)are added to guard against data transmission errors.

In one embodiment, the power and signaling pulses described above arecarried between the CRM module and the measurement module(s) via atwo-conductor lead. Each conductor is internally connected within bothmodules. The first conductor may also be attached to the “indifferent”electrode, which defines the baseline potential for sensing and pacing.In one embodiment, a low impedance common conductor such as DFT wireextends between the indifferent electrode and the measurement module inorder to prevent the signaling pulses from affecting the sensing of theelectrogram. In another embodiment, the indifferent electrode isconnected to the sensing/pacing module by a third conductor. The secondconductor is electrically isolated from the body. Advantageously, thisconductor is physically contained by the outer coaxial first conductorand the housings at each end. To ensure electrical isolation at the CRMpackage, a spring contact without a setscrew and seal are provided onthe second inner conductor rather than on the outer conductor as iscustomary in CRM devices. The measurement module stores electricalenergy from one or more power pulses and applies an appropriate pacingpulse to a pacing electrode when a pacing command is received from theCRM module during the download interval. Importantly, the distancebetween the pacing electrode and the indifferent is substantiallyreduced, thereby greatly reducing any induced voltages during magneticresonance imaging (MRI) or electrocautery procedures. In one embodiment,the sensor/pacing module stores electrical energy from one or more powerpulses and applies an appropriate pacing pulse to the pacing electrodewhen a pacing command is received from the CRM module, for example,during the download interval. In an alternative embodiment, pacemakertiming is provided by circuitry within the sensor/pacing module,autonomous from the CRM module. In both embodiments, the sensor/pacingmodule may generate or store electrical energy for application of anappropriate pacing pulse to the pacing electrode at intervals defined byeither the CRM module or the circuitry within thesensor/pacing/measurement module itself. In another embodiment, thepacing interval is modified or synchronized with a second digitalelectrode in another location by the generator module by downloading theappropriate command to the sensor/pacing/measurement module.

In one embodiment, the circuitry includes current and voltage limitingfeatures known to those skilled in the art to provide protection fromdefibrillator discharges, either from an external or implantabledefibrillator. In one embodiment, series-connected oppositely orientedzener diodes are provided for defibrillation protection as described,for example, by Langer (U.S. Pat. No. 4,440,172, incorporated byreference herein).

Referring to FIG. 25, three embodiments are described to implement ahybrid approach for performing pacing and physiological sensing usingthe same lead.

In the first embodiment, the output voltage during the pacer pulse isprovided by a CRM device 306. Alternatively, in another embodiment, anoutput voltage storage capacitor and a charge pump are provided by adevice 320, such as a POD.

Sensing may be performed according to at least three differentembodiments. In one embodiment, the circuitry is located in a device320, such as the POD, and a digital signal is provided when a p-wave isdetected. In the second embodiment, an electrode 328 is switched byswitch 322 onto the lead conductor 324 either before or after the outputcapacitor 326, and the CRM device 306 contains the sensing circuit. Inthis embodiment, the lead 324 may be pre-charged to the electrodevoltage to avoid generating signals on the electrode 328. A thirdembodiment is a hybrid of the first two. In the third embodiment, anIEGM signal is amplified by an amplifier 330 and applied to the lead324. For all three of these options, IEGM sampling is time-multiplexedin the frame sequence.

Either on-chip or back-to-back Zener diodes 332 are provided in thedevice 320, thereby keeping the RF path (during MRI) small in order toimprove immunity.

2. Upgrade from Stand-Alone to Combination System

Referring now to FIG. 26A, in one embodiment, the same sensor and lead318 can be used either as part of a Stand-Alone system (such as a heartmonitoring system, pressure monitoring and feedback system, HEARTPOD™,POD, or apparatus for treating congestive heart failure, as describedabove) or as part of a combination system that includes a CRM orautomated therapy system. This flexibility allows for the implantationof a Stand-Alone sensor that can be “upgraded” to include pacing and/ordefibrillation therapy if the need arises without having to implant anadditional lead. The combination system also allows the communicationcoil 302 of the apparatus for treating congestive heart failure (such asthat described above with reference to FIG. 4) to be removed andreplaced with a CRM 306. Furthermore, in one embodiment, the sensorelectronics (which in one embodiment are located in a distal sensorpackage implanted within the patient's heart, as schematicallyillustrated in FIG. 26B) include the pace/sense circuitry that allows itto be used as a smart “digital” electrode in conjunction with a CRMdevice, as described below, to provide a digital pacemaker.

In an alternate embodiment, an additional lead conductor is included toallow operation with pacing and sensing electronics located within theCRM housing 306 of a CRM device. In one embodiment, a sensor or sensormodule 320 is coupled to the distal end of a lead 318, which has aproximal IS1 connector 316, as is familiar to those of skill in the art.In one embodiment, an upgrade is performed by surgically opening thesubcutaneous pocket, unplugging the IS1 connector 316 from the RF coilantenna 302, or pressure monitoring and feedback implanted module, andplugging the lead 318 into an IS1 port 317 of a CRM housing 306, asdescribed in greater detail below.

In one embodiment, the sensor is externally powered either by a tunedcoil 303 (Stand-Alone mode) at 125 kHz (although any other suitablefrequency could be used) or “power” pulses (CRM mode) at a framefrequency. In the Stand-Alone mode, data from the sensor is telemeteredto a patient advisory module (not shown) using reflected impedance.Other telemetry schemes may also be employed, such as disclosed, forexample, in U.S. Pat. Nos. 4,681,111 and 5,058,581 to Silvian,incorporated herein by reference. Electronics provided with the device,such as the POD or distally implanted sensor module, contain circuitrythat detects whether an incoming signal is a 125 kHz signal (as isprovided by the pressure monitoring and feedback implanted module, inone embodiment) or a frame power pulse (as is provided from a CRMdevice, in one embodiment) at a frequency between 500 Hz and 20 kHz.This autosensing functionality allows the pressure monitoring andfeedback system described herein to be “upgraded,” whereby theadditional functionality of a CRM system, such as a pacemaker ordefibrillator or other such device, is able to be provided by merelychanging, or swapping one implanted component, or module, with another.At least two methods are provided for determining which mode(Stand-Alone or combination) is operable, as described below withreference to FIGS. 26A-D. One method is based on frequencydiscrimination and the other is based amplitude discrimination. In bothcases, the signals are half-wave rectified by rectifier 300 to providepower for the sensor (and pace/sense) electronics. As is recognized bythe skilled artisan, full-wave rectification could be employed as analternative. Two embodiments of rectifier 300 are provided in FIGS.26C-D.

In one embodiment, in the Stand-Alone mode (e.g., when a CRM 306 is notpresent), the 125 kHz signal is output from a tuned coil 302 thatresides in a subcutaneous pocket. The 125 kHz signal is rectified toprovide DC power for the sensor electronics of the sensor module 320 anda 125 kHz clock for operation and timing. A shorting FET, which in oneembodiment is located within communications module 304, is placed acrossthe 125 kHz input to provide a reflected impedance signal that can bedetected by the external device for telemetry of the sensor(s) output.The FET is disabled after power up until the POD has determined that theStand-Alone mode is operable. Although full wave rectification could beused, in one embodiment, half wave rectification is employed. Detectionof the unused half cycle is one of the methods used to differentiatebetween the two modes of operation. In one embodiment, power is turnedoff to the pacing and sensing electronics in the Stand-Alone mode.

In one embodiment, in the CRM mode, the sensor lead 318 is attached to aCRM device 306 that provides a power pulse at a fixed frame rate, a pacetrigger signal, and apparatus for changing memory registers in the POD.The power pulse is rectified to provide DC power for the PODelectronics. The reflected impedance shorting FET used in theStand-Alone mode is disabled at power up and in CRM mode. A frame clockdetector 308 is employed to obtain the frame clock that is input to aDPLL 310 (digital phase lock loop). The DPLL 310, by way of example,includes or is coupled to an oscillator 311 with electronic frequencyadjustment with its output used for operation and timing for the PODelectronics. This clock is fed into a divide by N counter (or bitcounter) 312 through a clock select switch 314. The output of the bitcounter 312 is coupled to the other input of the DPLL 310, whose outputis connected to the frequency adjustment of the oscillator 311. Thedivide by N counter 314 output may be coupled directly to the up/downcounter 312 (or bit counter 312), or may be coupled to a clock selectmodule 314 which is coupled to the bit counter 312, as shown in FIG.26B. This provides for an internal clock, which is N times the frameclock and is synchronized to the frame clock. In another embodiment, ananalog PLL is used instead of a digital PLL. The DPLL 310 also providesa signal to indicate the mode of operation (the frequency discriminationmethod). If the DPLL 310 is locked at its limit (no sync), thenStand-Alone operation is indicated. In the CRM mode, the CRM device 306goes to high impedance between power pulses during the upload period,thereby allowing the POD to send sensor output(s) and a pacingsense-detect signal to the CRM device 306.

Since the physical connection is different between the two modes ofoperation, the detection mechanisms for mode determination can beoptionally latched at power up and then disabled to conserve power.

One embodiment of the present invention provides for a novel variationof a standard IS1 header 316. In conventional IS1 headers, typically aspring connector is employed for the outer conductor and a setscrew isused for the inner conductor. Both the 125 kHz for the Stand-Alonedevice and the digital power/signaling signals of the combination deviceneed to be isolated from the body and especially the heart in afail-safe manner. Advantageously, in one embodiment of the presentinvention, the active conductor is the inner conductor of a coaxial leadand a spring connector is used for the inner conductor in the IS1 header316. This assures that, even in a damaged lead or leaking setscrew seal,all leakage paths to the body are completely surrounded by the commoncoax outer conductor, and therefore isolated from the body.

In one embodiment, the system is designed to operate in at least twodifferent configurations, and in at least two modes of operation. Afirst mode is the “Stand-Alone Configuration.” A second mode is “the CRMCombination” (or “Combination Configuration”). One advantage of amulti-configuration system is that it allows the device to be implantedas a Stand-Alone system for CHF therapy and later to be upgraded for usewith a CRM device if the patient's condition changes. In the CombinationConfiguration, in one embodiment, the sensor module 320 acts as apace/sense electrode for the CRM device.

In one embodiment, there are three modes of operation based on theconfiguration: (1) A “Power-Up Mode” which is used to automaticallydetect whether the Stand-Alone Configuration or the CombinationConfiguration is present. This mode is entered into when the power isapplied to the sensor module 320. As described below by way of example,at least two alternative methods are described for detecting theconfiguration. Alternative methods will be apparent to one skilled inthe art; (2) A Stand-Alone Configuration; and (3) A Combinationconfiguration.

In one embodiment, the CRM module logic includes logic to detect anyproblems with the sensor module 320. Should any unrecoverable problem bedetected, the CRM module (which in one embodiment can optionally belimited to be under physician supervision) stops the power pulses to thesensor module 320 and restarts, thus allowing for a new power-upsequence.

Communication block: In one embodiment, a communication block 304 isprovided. In one embodiment, the communication block 304 is responsiblefor the bidirectional communication. The Mode and PwrUp inputs definehow the device operates. Incoming communication in a preferredembodiment is by FSK on the 125 kHz carrier for the Stand-AloneConfiguration and by digital command signals between power pulses forthe Combination Configuration. Outgoing communication in one embodimentis by reflected impedance for the Stand-Alone Configuration and bydigital signals between power pulses for the Combination Configuration.During the power-up mode, all outgoing communication is suppressed. Thefigure for Combination Configuration signals depicts a RZ code. Oneskilled in the art will understand that other encoding methods, such asNRZ, Manchester, etc., can also be used in accordance with severalembodiments of the current invention.

Voltage Detector Block: In one embodiment, a voltage detector block 322is provided. In one embodiment, the voltage detector block 322 detectsthe operating configuration after power is applied (during the power-upmode). In one embodiment, it only needs to be powered during this brieftime and can be disabled to conserve power. The voltage detector block322 detects whether or not there are 125 kHz excursions above Vdd, whichmay occur in the Stand-Alone Configuration.

Clock Detector Block: In one embodiment, a clock detector block 308 isprovided. In one embodiment, this block 308 is a comparator with twothresholds that outputs a digital clock signal from the signal on thelead. In the Stand-Alone Configuration, the threshold is set to Vdd andthe output is a 125 kHz square wave. In both the CombinationConfiguration and Power-Up Mode, the threshold is set to approximately0.5V above Vss (although other thresholds may be used) and the output isused to recover the frame sync which are the power pulses in thecombination mode and 125 kHz during the power-up mode in the Stand-AloneConfiguration. One reason for the 0.5 V threshold is to allow signalingpulses to have lower amplitude than the power pulses and will not beerroneously detected as clock pulses (and will also dissipate lesspower). Alternatively, the midpoint supply voltage may be used as athreshold, with equal amplitude power and signaling pulses, providedthat the DPLL 310 and related timing provides for a defined gap betweenthe last signaling pulse and the next power pulse.

Clock Divider Block: In one embodiment, a clock divider block 314 isprovided. In one embodiment, this block 314 divides down the 125 kHz toprovide a bit clock in the Stand-Alone configuration. It is disabled inthe CRM configuration.

Oscillator block: In one embodiment, an oscillator block 311 isprovided. In one embodiment, this block 311 contains a capacitor that ischarged up from Vss to a settable threshold voltage. A short reset pulseis provided to fully discharge the capacitor after the threshold reachedand if a reset pulse is provided. The threshold is determined by theoscillator control lines that specify to either to increase or todecrease the threshold by a small delta V. In an alternative embodiment,the capacitor is arranged in a binary array and the DPLL 310 is anup/down counter.

Clock Select Block: In one embodiment, a clock select block 314 isprovided. In one embodiment, this block 314 switches the bit clock tothe sensor module's internal oscillator output for the CRM CombinationConfiguration and during the power-up mode. For the Stand-AloneConfiguration, the bit clock 314 is switched to the output of the 125kHz clock divider.

Bit Counter Block: In one embodiment, a bit counter block 312 isprovided. In one embodiment, this block 312 is a divide by N counterthat is reset by the Frame sync in the CRM configuration and duringpower-up. It provides the bit timing sequence for each frame. Duringpower-up, in the Stand-Alone Configuration, it is substantially heldreset by the 125 kHz “frame sync” pulses.

DPLL Block: In one embodiment, a DPLL block 310 is provided. In oneembodiment, the DPLL 310 provides the feedback to control the internaloscillator frequency to be N times the frame sync. In one embodiment, italso determines the configuration during power-up mode by detecting thatthe Bit counter 312 is stuck reset.

Rectifier Block: In one embodiment, a rectifier block 300 is provided.Two alternative embodiments are shown in greater detail in FIGS. 26C-D.In the embodiment of FIG. 26C, Vdd is tied to the outer lead windingwhich is tied to the Indifferent Electrode. A schottky diode is providedto protect the CMOS from the positive swing on the inner “Lead” windingin the Stand-Alone configuration. Alternatively, a full wave rectifiercould be used. A separate charge pump and pacing output voltage storagecap is provided to generate and store the pace voltage. In the secondrectifier embodiment, which is illustrated in FIG. 26D, the charge pumpand storage cap are omitted from the sensor module. Instead, a MOSswitch is provided between Vdd and the Indifferent. This switch isnormally ON but is switched OFF during a pacer pulse so that the pacevoltage is stored in the CRM device and switched out to the distalelectrode. Additional circuitry is provided to handle start-up and wellswitching issues.

Control Circuit Block: Referring back to FIG. 26B, in one embodiment, acontrol circuit block 324 is provided. In one embodiment, this block 324provides substantially all the memory storage, logic and timing requiredfor operation.

Measurement Circuit Block: In one embodiment, a measurement circuitblock 326 is provided. In one embodiment, this block 326 providessubstantially all the measurement circuitry to measure pressure,temperature, etc.

Input Amp & Filter Block: In one embodiment, an input amp & filter block328 is provided. In one embodiment, this block 328 contains an ACcoupled amplifier, filter and window comparator for the detection ofheart depolarization signals (P-wave and/or R-wave). The circuits forthis function are well known in the art. This block 328 is shownconnected to a separate sensing electrode. Normally the pacing andsensing electrode are the same, which is still possible in thisinvention by merely shorting these points together. Advantageously, oneembodiment provides for the possibility of separate pacing and sensingelectrodes without having to have a separate lead conductor and extraconnector pin. This allows each electrode to be optimized independentlyfor each electrode. In addition, the recovery discharge voltage iseliminated on the sensing electrode, allowing for sensing of the inducedP or R-wave for capture verification and/or threshold tracking. Thisadvantage is due to the inclusion of the pacing & sensing electronicsremotely in the sensor module. If two distinct electrodes are employed,additional defibrillator protection may be needed for the senseamplifier. This protection is relatively easy because the impedances canbe much higher and the induced currents are easily handled.

Defibrillation Protection Block: In one embodiment, a defibrillationprotection block 330 is provided. In one embodiment, this block 330 iscomposed of two back-to-back zener diodes or other method as is known inthe art.

One embodiment of an upgradeable system is illustrated in FIG. 28 andFIG. 29. The system of FIG. 28 illustrates a “Stand-Alone” embodiment,and includes an implantable housing 400 coupled to an implantable lead402 with a connector 404. In one embodiment, the housing 400 is thehousing 7 as described above. In another embodiment, the lead 402 is thelead 318 or lead 10 as described above. In one embodiment, connector 404is the IS1 header 316, IS1 port 317, or connector 10, as describedabove. The connector 404 may be any connector known to those of skill inthe art used to couple an implantable lead to an implantable housing.

The lead 402 is connected to a sensor module (not shown) as described ingreater detail above. The lead 402 is also electrically coupled to anindifferent electrode 406, as is well known to those of skill in theart. The implantable housing 400 of the Stand-Alone embodiment includesan antenna 408. In one embodiment, the antenna 408 is the antenna 162 orcoil 302 as described in greater detail above. The antenna 408 may beany coil of wire as is known to those of skill in the art, which may beused for telemetry communications with an external device, such as apatient advisory module (not shown), as described in greater detailabove with reference to FIGS. 4 and 5. In one embodiment, the antenna408 is coupled to the lead 402 via the connector 404, and functions asdescribed above.

One embodiment of a “combination” unit is described with reference toFIG. 29. As described above, in one embodiment, when the Stand-Aloneunit is upgraded to provide CRM functionality in addition to left atrialpressure sensing and patient feedback, the housing of the Stand-Alonesystem may be exchanged with the housing of a combination system withouthaving to provide an additional lead for cardiac rhythm management.

As illustrated in FIG. 29, in one embodiment, the housing 400 of thecombination unit is coupled to a lead 402 via a connector 404 asdescribed above. In one embodiment, the lead is coupled to anindifferent electrode 406, also as described above. In one embodiment,the housing 400 of the combination unit is the same as the housing 400of a Stand-Alone unit, or CRM housing 306, as described in greaterdetail above.

The housing 400 of the combination unit includes an antenna 408, battery410, telemetry module 412, communication and power pulses module 414,programming module 416, and pacing circuitry 418. The battery 410provides power to the components within the housing 410, as well asthose within the sensor module (not shown), as describe above. Thetelemetry module 412 provides communication between the combination unitand the patient advisory module (not shown). The communication and powerpulses module 414 control communication between the sensor module (notshown) and the housing 400 components as well as power distribution tothe sensor module from the battery 410. Programming module 416 providesprogramming control over the system, including the pacing module 418,which controls the transmission of electrical pulses or stimuli asrequired by the CRM device.

FIG. 29 illustrates one embodiment of a CRM Combination configuration.In this configuration, the housing 400 contains a battery 410 thatpowers both the CRM device and the sensor module (not shown). Thecommunication and power pulse circuit 414 provides power to andcommunicates with the sensor module via the lead conductor 402 using, inone embodiment, for example, the coding scheme described with respect toFIG. 24. The communication circuit 414 also decodes physiological sensorsignals, such as pressure signals, a-wave and/or p-wave sense signalsreceived from the sensor module via the lead 402. Sense signals receivedby the communication circuitry 414 are passed to the pacing circuitry418 where they are used to determine if and when to provide a pacingstimulus.

In one embodiment, the pacing circuitry 418 triggers a pacing stimulusby sending a signal to the communication circuitry 414, which sets theappropriate pulse trigger bit to the sensor module as described abovewith respect to FIG. 24. In one embodiment, the pacing circuitry 418delivers the pacing stimulus to the lead 402 a predetermined intervalafter setting the pulse trigger bit, and commanding the sensor module toallow the pacing stimulus to pass from the lead 402 through the sensormodule electronics to the pacing electrode. In another embodiment, thepacing stimulus is applied to the pacing electrode from a storagecapacitor within the sensor module when a pulse trigger bit is receivedby the sensor module from the communication circuitry 414.

In one embodiment, various operational modes and parameters areprogrammed using an external programming device (not shown) thatcommunicates with the implanted pacemaker transcutaneously usingtelemetry system 412, which decodes programming commands from aprogrammer and passes them to the programming circuitry 416. In oneembodiment, physiological sensor signals, such as but not limited topressure, temperature, or internal electrocardiogram signals, are passedfrom the communication circuitry 414 to the telemetry circuitry 412 fortelemetry to the external patient advisory module, such as the patientadvisory module illustrated and described above with reference to FIG.4. In one embodiment, physiological sensor signals are also communicatedfrom the communication circuitry 414 to the programming circuitry 416,where they are used to at least partially to control the operation ofthe pacemaker in response to the patient's condition.

3. Automated Therapy

According to one embodiment of the current invention, a method fortreating cardiovascular disease in a medical patient includes implantinga physiological sensor package and a therapy delivery unit (e.g., the“treatment system”) within the patient's body, operating thephysiological sensor package to generate a signal indicative of aphysiological parameter, communicating the signals indicative of thephysiological parameters to a signal processing apparatus, operating thesignal processing apparatus to generate a signal indicative of anappropriate therapeutic treatment, and communicating to the patient thesignal indicative of the appropriate therapeutic treatment. The patientmay then administer to him or herself the prescribed therapeutictreatment indicated by the signal or instructions. In anotherembodiment, the signal indicative of the appropriate therapeutictreatment is communicated to an automated therapy unit to generate anautomatic therapy regime.

a. Dynamic Prescription

In one embodiment, the automatic therapy regime is based upon aprogrammed dynamic prescription. “Dynamic prescription,” as used herein,shall mean the information that is provided to the patient for therapy,including instructions on how to alter therapy based on changes in thepatient's physiologic parameters. The instructions may be provided by aphysician, practitioner, pharmacist, caregiver, automated server,database, etc. The information communicated to the patient includesauthorizing new prescriptions for the patient and modifying thepatient's medicinal dosage and schedule. The “dynamic prescription”information also includes communicating information which is not“prescribed” in its traditional sense, such as instructions to thepatient to take bed rest, modify fluid intake, modify physical activity,modify nutrient intake, modify alcohol intake, perform a “pill count,”measure additional physiological parameters, make a doctor'sappointment, rush to the emergency room, call the paramedics, etc. Oneskilled in the art will understand that numerous other instructions maybe beneficially provided to the patient predicated at least in part uponmeasurement of one or more physiological parameters in accordance withvarious embodiments of the present invention.

b. Therapy Delivery Units

According to another embodiment, a therapy delivery unit is provided,including but not limited to a system for releasing bioactive substancesfrom an implanted reservoir, a system for controlling electrical pacingof the heart, and cardiac assist devices including pumps, oxygenators,artificial hearts, cardiac restraining devices, ultrafiltration devices,intravascular and external counterpulsation devices, continuous positiveairway pressure devices, and a host of related devices for treatingcardiovascular conditions where knowledge of the left atrial pressurewould be beneficial for optimal therapy delivery. Cardiac electricalpacing may be controlled in response to changes in physiologicalparameters in accordance with the present invention by, for example, AVdelay optimization or any number of other methods, as are well known toone skilled in the art of cardiology.

According to one embodiment of the invention, the therapy delivery unitis implanted according to the methods described herein for the pressuretransducer.

i. Drug Infusion

In one embodiment of the invention, a drug delivery unit is provided. Inthis embodiment, intravenous or subcutaneous, bolus or continuousinfusion of drug from an implantable drug delivery unit can be triggeredor regulated by the signal processing apparatus when certain predefinedconditions are met. In one embodiment, automatic drug delivery or othertherapeutic measure is used as a last resort “rescue mode” when themonitored physiological parameters indicate the patient's conditionrequires urgent therapeutic response. Typically, in “rescue mode”, thepatient's condition is not amenable to a change in oral medication dose(see “Dynamic Prescription”). Thus, in one embodiment, this inventionincludes both the dynamic prescription with patient signaling, andautomated therapy via electrical stimulation, drug infusion, or othertherapy delivery unit. Drugs that may be so administered include but arenot limited to natriuretic peptides (e.g., Natricor), diuretics (e.g.,furosimide), and inotropes (e.g., epinephrine, norepinephrine, dopamine,dobutamine, milrinone). In one embodiment, rescue mode emergency druginfusion, defibrillation, or other therapy is performed automaticallybased at least in part on signals indicative of the patient's conditionderived from the one or more sensors of the invention. In anotherembodiment, rescue mode therapy is initiated by the present inventiononly after receiving doctor authorization to deliver the therapy. In oneembodiment, doctor authorization is given by entering a password intothe external patient signaling/communication module. This permitspotentially dangerous emergency therapy to be delivered only afterconsultation with and authorization by a qualified healthcareprofessional.

In one embodiment, dosimetry for multiple drugs or other associatedtherapeutic devices is relayed based on parameter values as input to aparameter-driven prescription. In one embodiment, the system essentiallyreplicates, in the home setting, the way inpatients are managed based ontheir doctor's standing orders in the Intensive Care Unit (ICU) of ahospital. In the ICU, nurses periodically look at real-time physiologicvalues from diagnostic catheters, and administer medications based onpredetermined orders by the patient's attending physician. Oneembodiment of the present invention accomplishes the same thing. In oneembodiment, wireless communications technology is integrated withdiagnostic and treatment methods that are well established incardiology. As such, the system is designed to be convenient andtime-efficient for both the patient and his physician. The combinationof monitoring key physiologic parameters and the patient's ownphysician's prescription drive a real-time feedback loop control systemfor maintaining homeostasis. Thus, in one embodiment, the systemcomprises an integrated patient management system tightly and directlylinking implantable sensor diagnostics with pharmacologic and othertherapies. As a result, this therapeutic approach enables better, morecost effective care, improves out-of-hospital time, and empowerspatients to play a larger and more effective role in their ownhealthcare.

In one embodiment, a portable system for continuously or routinelymonitoring one or more parameters indicative of the condition of apatient is provided. Depending upon changes in the indicated condition,the system determines, based on parameter-driven instructions from thepatient's physician, a particular course of therapy. The course oftherapy is designed to manage or correct, as much as possible, thepatient's chronic condition. In one embodiment, the system communicatesthe course of therapy directly to the patient or to someone who assiststhe patient in the patient's daily care, such as, for example, but notlimited to, a spouse, an aid, a visiting nurse, etc.

C. Telemetry

In one embodiment of the invention, one or more signals are communicatedbetween the permanently implanted components of the system and acomponent of the system external to the patient's body. In oneembodiment, signaling from the implanted to the external components isachieved by reflected impedance using radio frequency energy originatingfrom the external device, and signaling from the external components tothe internal components is achieved by frequency or amplitude shiftingof radio frequency energy originating from the external device. Thus, inthis embodiment, the current invention allows for telemetry of data fromwithin the heart without transmitting radio frequency energy from theimplanted device, advantageously resulting in significantly reducedpower consumption compared to implants that perform telemetry bytransmitting signals from within the body.

In another embodiment, signaling from the implanted to the externalcomponents is achieved through the metal housing of the implanted deviceusing the method of Silvian (U.S. Pat. No. 6,301,504) incorporated byreference in its entirety herein.

In yet another embodiment, signaling from the implanted housingcontaining components of a CRM device is achieved via an antennaembedded within a dielectric around the periphery of the housing, astaught, for example, by Amundson et al. in U.S. Pat. No. 6,614,406,included herein by reference.

D. Power

In one embodiment of the invention, the implanted apparatus is poweredby a battery located within an implanted housing, similar to that of acardiac pacemaker, as is well known in the art of cardiac pacing. Inanother embodiment, the implanted apparatus is powered by an externalpower source through inductive, acoustical or RF coupling. In oneembodiment, power is provided to the implanted device using 125 kHzemissions emitted from an electrical coil placed outside the body. Inone embodiment power and data telemetry are provided by the same energysignal. In one embodiment of the system a second electrical coil isimplanted inside the body at a location under the skin near thepatient's collarbone, similar to the placement of the generator housingof an implantable pacemaker.

E. Physical Location of System Components

In one embodiment of the present invention, the apparatus for diagnosingand treating cardiovascular disease is modular and consists of aplurality of modules. Each module contains hardware, and may contain oneor more software programs. The component modules can be physicallylocated in different places and their functions can differ dependent onthe particular design of the modules. FIG. 4 shows one embodiment of thecurrent invention, in which the first implantable module 5 of theapparatus is implanted within the patient. A patient advisory module 6is located external to the patient's body and generally resides with thepatient or his direct caregivers. A third module (not shown in FIG. 4)may reside with the physician. Each module performs multiple functionsand some of the functions may be performed on multiple modules. In oneembodiment, the modules consist of component sub-modules that perform aparticular function, such as described above.

1. Leads

Although the pressure transducer in the embodiment produces anelectrical signal indicative of pressures in its vicinity and,accordingly, an electrical lead is used to transmit the signals to theelectronic circuitry, other types of pressure transducers may be used aswell. For example, the pressure transducer and lead might comprise atube filled with an incompressible fluid leading from the site in thebody where the pressure is to be measured back to a transducer inanother location. Signals in the form of pressures in the incompressiblefluid indicate pressures at the site of interest, and those pressuresare sensed by the transducer and utilized by the electronic circuitry ingenerating signals indicative of appropriate therapeutic treatments.Signals in other forms may be used as well and may be transmitted, forexample, by fiber optic means, or by any other suitable electrical,electro-mechanical, mechanical, chemical, or other mode of signaltransmission.

Moreover, although the signal lead in one embodiment is of anappropriate length so that the housing containing the electroniccircuitry can be implanted in the region of the patient's shoulder, inalternative embodiments the lead may be of virtually any useful length,including zero. In one embodiment, an integrated unit is used in whichthe pressure transducer is disposed directly on the housing and theentire device is implanted inside or very near to the site at whichpressure measurement is desired, for example the left atrium of thepatient's heart.

II. SYSTEM OPERATION A. Signal Processing

FIG. 27 is a schematic diagram of operational circuitry that in oneembodiment is located inside the housing 7 and is suitable for use inaccordance with one embodiment of the present invention. The apparatusdepicted in FIG. 27 includes digital processors, but the same conceptcould also be implemented with analog circuitry, as is well known tothose of skill in the art.

As described above, in one embodiment, the system of the inventionincludes a pressure transducer 73 permanently implanted to monitor fluidpressure within the left atrium of the patient's heart. Moreover, thesystem may include one or more additional sensors 75 configured tomonitor pressure at a location outside the left atrium, or a differentphysical parameter inside the left atrium or elsewhere. For each sensor73, 75, a sensor lead 77, 80 conveys signals from the sensor 73, 75 to amonitoring unit 82 disposed inside the housing of the unit.Alternatively, several sensors may be located in a compact sensorpackage or sensor module as, for example, illustrated in FIGS. 1, 2, 4,22 and 23. In this case, the several sensors may share a single sensorlead for conveying signals from the sensors to the monitoring unit or atelemetry antenna. It should also be noted that the sensor leadconnecting the pressure transducer to the monitoring apparatus mightalso be combined with or run parallel to another lead such as anelectrical EKG sensor lead or a cardiac pacing lead, either of whichmight be placed in or near the left atrium.

In one embodiment, when the signal from the left atrial pressuretransducer 73 enters the monitoring unit 82, the signal is first passedthrough a low-pass filter 85 to smooth the signal and reduce noise. Thesignal is then transmitted to an analog-to-digital converter 88, whichtransforms the signals into a stream of digital data values, which arein turn stored in digital memory 90. From the memory 90, the data valuesare transmitted to a data bus 92, along which they are transmitted toother components of the circuitry to be processed and archived. Thestream of binary digital values may be immediately transmitted to atelemetry device external to the patient one bit at a time as they aregenerated from the most significant bit to the least significant bit bya successive approximation analog-to-digital converter. An additionalfilter 95, analog-to-digital converter 97, and digital memory area 100may be provided as shown for each optional sensor 75 whenever such asensor 75 is present. In another embodiment, several sensors share oneanalog-to-digital converter.

In one embodiment, the digital data on the data bus 92, are stored in anon-volatile data archive memory area 103. The archive 103 stores thedata for later retrieval, for example, by a physician at the patient'snext regularly scheduled office visit. The data may be retrieved, forexample, by transcutaneous telemetry through a transceiver 105incorporated into the unit. The same transceiver may serve as a routefor transmission of signals into the unit, for example, forreprogramming the unit without explaining it from the patient. Thephysician may thereby develop, adjust, or refine operation of the unit,for example, as new therapies are developed or depending on the historyand condition of any individual patient. By way of an additionalexample, reprogramming the implanted device could include changing thesampling frequency for digitizing the pressure, IEGM or other waveforms,or selecting which sensor data is to be monitored. Devices fortranscutaneous signal transmission are known in the art in connectionwith pacemakers and implantable cardiac defibrillators (collectivelyknown as cardiac rhythm management apparatus), and the transceiver usedin the present invention may be generally similar to such knownapparatus.

In one embodiment of the present invention, the digital data indicativeof the pressure detected in the left atrium, as well as datacorresponding to the other conditions detected by other sensors, wheresuch are included, are transferred via the data bus 92 into a centralprocessing unit 107, which processes the data based in part onalgorithms and other data stored in non-volatile program memory 110. Thecentral processing unit 107 then, based on the data and the results ofthe processing, sends an appropriate command to a patient signalingdevice 113, which sends a signal understandable by the patient and basedupon which the patient may take appropriate action such as maintainingor changing the patient's drug regimen or contacting his or herphysician.

Circuits for extracting relevant components from a pressure waveform arefamiliar to those skilled in the art. For example, a low pass filterelement may be used to extract the long-term average, or “DC” component.In one embodiment, the outputs of overlapping low pass filters, onedesigned to include only frequencies lower than respiratory cyclefrequencies, and the other designed to include respiratory but notcardiac cycle frequencies, are sampled at a fixed time in each cardiaccycle and subtracted to derive the respiratory component. In general,the respiratory contribution to the waveform is negative duringinspiration and positive during expiration, with a mean contribution ofzero. Thus, the long-term average of the pressure waveform is equal tothe average of the cardiac component. The term of the long-term averageis chosen to be long compared to the respiration rate but short comparedto the rate of mean pressure change due to changes in a change in thepatient's condition, so that slowly changing physiological informationrelevant to managing the patient's condition is not lost.

B. Signal Communication

In several embodiments of the invention, the patient signaling device113 comprises a mechanical vibrator housed inside the housing of thesystem. In one embodiment, the vibrator delivers a small, harmless, butreadily noticeable electrical shock to the patient. In some embodiments,a low power transmitter configured to transmit informationtranscutaneously to a remote receiver, which could include a displayscreen or other means for communicating instructions to the patient. Inone embodiment, the system includes communication devices forcommunicating information back to a base location. These communicationdevices include, but are not limited to cellular or land-line telephoneequipment or a device connected to the Internet, for communicatinginformation back to a base location. In one embodiment, this is used, totransmit information concerning the patient's condition back to ahospital or doctor's office, or to transmit information concerning thepatient's prescription usage back to a pharmacy.

In one embodiment, the signal processing and patient signalingcomponents of the invention are combined into a patient advisory module,external to the patient's body. The patient advisory module furthercomprises a telemetry module to receive pressure and other physiologicaldata from the implanted sensor system via wireless telemetry. Thisconfiguration has the advantage that the external device may be based inpart on a general purpose computer such as a personal data assistant(PDA), allowing increased flexibility and complexity in signalprocessing and prescription algorithms. An additional advantage is thatit provides essentially unlimited storage for digital physiological datafrom the patient, as well as for information on medications and otherrelevant information to help the patient and physician manage congestiveheart failure.

Yet a further advantage of the externalized patient signaling devicecomponent is that a much richer and easier to use interface with thepatient is facilitated using a display screen and/or audio communicationwith the patient. In one embodiment, a reminder function is incorporatedin the external device such that the patient is prompted to initiatemeasurement just prior to scheduled medications or other therapy. Thepatient is then advised of the appropriate doses of medications and/orother therapies based on the measurements and his physician's dynamicprescription.

In one embodiment, the patient advisory module is external and serves asa treatment and medications record. In this use, the patient will beasked to verify which of the prescribed medications were taken and whichwere, for whatever reason, were skipped, thus creating a record ofcompliance with the dynamic management program. This function willpermit the physician to better manage the patient and, additionally,will improve patient compliance. Yet another advantage of theexternalized patient advisory module is that it can be easily integratedwith a cellular telephone or PDA/cell phone combination, allowingautomated telemetry of alerts and/or physiological data to a remotehealth care provider such as the patient's physician, hospital, nursingclinic, or monitoring service.

Apparatus as described herein may also be useful in helping patientscomply with their medication schedule. In that case, the patientadvisory module could be programmed to signal the patient each time thepatient is to take medication, e.g., four times daily. This might bedone via an audio or vibratory signal as described above. In versions ofthe apparatus where the patient signaling device includes apparatus fortransmitting messages to a hand held device, tabletop display, oranother remote device, written or visual instructions could be provided.In one embodiment, apparatus generates spoken instructions, for example,synthesized speech or the actual recorded voice of the physician, toinstruct the patient regarding exactly what medication is to be takenand when.

Where the system includes apparatus for communicating information backto a base location, e.g., the hospital, doctor's office, or a pharmacy,the system in one embodiment, tracks the doses remaining in eachprescription and to reorder automatically as the remaining supply of anyparticular drug becomes low.

In one embodiment of this invention, the external device communicateswith a personal computer (PC) in the doctor's office either directlywhen the patient is present for an office visit, or via electroniccommunications, including, but not limited to, a telephone modem or theinternet. During this communication, data is uploaded from the externaldevice to the PC, including the records of physiological measurements,symptoms, and medication compliance, as well as information regardingthe operation and calibration of the implanted device. Software on thePC displays the patient information, and the doctor enters a new dynamicprescription or edits the existing one. The PC then downloads the new oredited dynamic prescription to the external device. Re-calibration ofthe pressure transducer in the external device may be performed relativeto a reference manometer in the physician's office.

In one embodiment, the physician's PC maintains a database of all thepatients under medical management by the physician using the device ofthis invention. The database includes the patients identifying,demographic, and medical information, the implantable device's uniqueidentification number. For each patient, the database maintains a recordof all data uploaded from the external device, device calibrationrecords, patient dynamic prescription records, and compliance records.

In one embodiment, data stored in the external patient advisory moduleis uploaded to the physician's PC at the time of the patient's regularoffice visit. The external device is placed in a data interface cradleconnected to the PC, and the data is transferred. In one embodiment ofthe data transfer, the external device is a modified personal dataassistant such as a PALM PILOT™ (Palm Computing, Inc.), and the datainterface cradle is the cradle used by such PDA devices for datasynchronization with a personal computer.

In another embodiment, the data from the external device is uploaded tothe physician PC via the Internet, telephone, or cellular telephonenetwork. In this case, the data may be uploaded at regular intervals, orwhenever the patient or physician determines there is a need forphysician review of the patient's management.

The prescription editor is a software program on the physician's PC thatallows the physician to create, view, and modify the dynamicprescription for each patient. The dynamic prescription may consist ofsets of prescribed treatments depending on the values of one or morephysiological measurements, and/or patient symptoms, and/or changesand/or rates of change of measurements or symptoms (collectively, inputparameters). A prescription editor allows the physician to definethresholds for each input parameter and to define the combination oftreatments to be administered for each possible combination of inputparameters. In one embodiment, the prescription editor has a graphicaluser interface that displays the possible combinations of inputparameter ranges and the corresponding treatments in a way that thephysician can clearly see that all possibilities have been definedaccording to his intended management of the patient. In anotherembodiment, the prescription editor provides for the entry and/orediting by the physician of a set of rules relating data collected fromthe patient and treatments to be administered or instructions to befollowed by the patient.

In one embodiment, the revised dynamic prescription and/or calibrationdata is downloaded from the physician's PC to the external device in thesame way that data is uploaded from the external device to thephysician's PC. In one embodiment, a unique identification number fromthe external device is used to verify the correct match between theprescription and the patient. This unique identification number isobtained by the external device from the implanted device, which has aunique identification number programmed into its integrated processorchip at the time of manufacture. In one embodiment, a 27-bit uniqueidentification code is permanently programmed into the implanted deviceat the time of manufacture. This identification number is sent alongwith data communicated from the implanted device to the external deviceto uniquely identify the implanted device to the external devicesoftware.

C. Power Management

In one embodiment, the circuitry of the invention may also include apower management module 115 configured to power down certain componentsof the system between times when those components are in use. Suchcomponents include, but are not limited to, analog-to-digital converters88, 97, digital memories 90, 100, and central processing unit 107, asshown in FIG. 27. This helps to conserve battery power and therebyextend the useful life of the device so that it can remain operationalinside the patient's body for extended periods between maintenance orreplacement. Other circuitry and signaling modes may be devised by oneskilled in the art.

In one embodiment, the implanted pressure monitor operates ontransmitted power from outside the body, eliminating the need for animplanted battery. This approach is particularly well suited whenperiodic, as opposed to continuous, monitoring is required. In oneembodiment, 125-kHz radio-frequency energy is transmitted from anexternal coil, through the patient's skin, and received by an implantedantenna coil connected to the electronics package of the implantablepressure monitor, as described above. The signal in the antenna coil isrectified and used to charge a capacitor, which in turn powers themeasurement electronics. Low power telemetry of the measured data isperformed by varying the impedance of the antenna coil circuit. In stillanother embodiment, the coil antenna is incorporated into or immediatelyadjacent to the pressure sensor within the heart.

III. EXAMPLES OF SYSTEM APPLICATION A. Example 1

Exemplary modes of operation for an embodiment of the system of theinvention are described as follows. The following Example illustratesvarious embodiments of the present invention and is not intended in anyway to limit the invention.

In one embodiment, the system is programmed to power up once per hour tomeasure the left atrial pressure and other conditions as dictated by theconfiguration of the particular system and any other sensors that mightbe present. Left atrial pressure measurements are taken at a 20-Hertzsampling rate for sixty seconds, yielding 1200 data values reflective ofthe fluid pressure within the left atrium. The central processing unitthen computes the mean left atrial pressure based on the stored values.Then, if the mean pressure is above a threshold value predetermined bythe patient's physician, the central processing unit causes anappropriate communication to be sent to the patient via the patientsignaling device.

A set of coded communications to the patient can be devised by thetreating physician and encoded into the device either at the time ofimplantation or after implantation by transcutaneous programming usingdata transmission into the non-volatile program memory 110 via thetransceiver 105. For example, assume that the physician has determinedthat a particular patient's mean left atrial pressure can be controlledat between 15 and 20 mm Hg under optimal drug therapy. This optimal drugtherapy might have been found to comprise a drug regimen including 5milligrams (mg) of Lisinopril, 40 mg of Lasix, 20 milliequivalents (mEq)of potassium chloride, 0.25 mg of Digoxin, and 25 mg of Carvedilol, alltaken once per day.

The patient is implanted with the device and the device is programmed asfollows. The device includes a pressure transducer implanted across theatrial septum such that the transducer responds to the difference inpressure between the right and left atria. This differential pressure isindependent of changes in atmospheric pressure, and in mostcircumstances is well correlated with, and thus indicative of, the leftatrial pressure. The device's programming provides for four possible“alert levels” that are specified according to mean differential atrialpressure detected by the transducer and computed in the centralprocessing unit, and that the patient signaling device is a mechanicalvibrator capable of producing pulsed vibrations readily discernable bythe patient.

At predetermined intervals, for example, hourly, daily, weekly, monthly,3-4 times per day, or in response to a detected event, in response to asymptom, or in response to an instruction, the device measures thepatient's mean left arterial pressure as described above, and determinesthe appropriate alert level for communication to the patient accordingto programming specified by the physician. For example, a mean leftatrial pressure of less than 15 mm Hg could be indicative of some degreeof over-medication and would correspond to alert level one. A pressurebetween 15 and 20 mm Hg would indicate optimal therapy and correspond toalert level two. A pressure between 20 and 30 mm Hg would indicate mildunder-treatment or mild worsening in the patient's condition, and wouldcorrespond to alert level three. Finally, a mean left atrial pressureabove 30 mm Hg would indicate a severe worsening in the patient'scondition, and would correspond to alert level four.

When the proper alert level is determined, the device sends a two-secondvibrating pulse to notify the patient that the device is about tocommunicate an alert level through a sequence of further vibrations. Afew seconds later, a sequence of one to four relatively short (onesecond) vibratory pulses, the number corresponding to the applicablealert level, are made by the device and felt by the patient. The patientcan easily count the pulses to determine the alert level, then continueor modify his own therapy with reference to a chart or otherinstructions prepared for him by the physician.

For example, two pulses corresponds to alert level two, an optimal ornear optimal condition for that particular patient. In that case, thedoctor's instructions tell the patient to continue his or her therapyexactly as before. The signal for alert level two is given once every 24hours, at a fixed time each day. This serves mainly to reassure thepatient that the device is working and all is well with his therapy, andto encourage the patient to keep taking the medication on a regularschedule.

One pulse, in contrast, corresponds to alert level one, and most likelysome degree of recent over-medication. The doctor's orders then notifythe patient to reduce or omit certain parts of his therapy until thereturn of alert level two. For example, the doctor's instructions mighttell the patient temporarily to stop taking Lasix, and to halve thedosage of Lisinopril to 2.5 mg per day. The coded signal is given to thepatient once every twelve hours until the return of the alert level twocondition.

Three pulses indicates alert level three, a condition of mild worseningin the patient's condition. Accordingly, the doctor's instructionsnotify the patient to increase the diuretic components of his therapyuntil alert level two returned. For example, the patient might beinstructed to add to his to his normal doses an additional 80 mg ofLasix, twice daily, and 30 mEq of potassium chloride, also twice daily.The level three alert signal would be given every four hours until thepatient's condition returned to alert level two.

Four pulses indicates alert level four, indicating a seriousdeterioration in the patient's condition. In this case, the patient isinstructed to contact his physician and to increase his doses ofdiuretics, add a vasodilator, and discontinue the beta-blocker. Forexample, the patient might be instructed to add to his therapy anadditional 80 mg of Lasix, twice daily, an additional 30 mEq ofpotassium chloride, twice daily, 60 mg of Imdur, twice daily, and tostop taking the beta-blocker, Carvedilol. The signal corresponding toalert level four would be given every two hours, or until the physicianwas able to intervene directly.

B. Example 2

In one embodiment, the system is configured as an externally poweredimplantable device with a sensor implanted in the intra-atrial septum.The pressure transducer of the sensor is exposed to the pressure in theleft atrium. In one embodiment, the sensor is anchored in the septumsuch that the pressure transducer is substantially flush with the leftatrial wall in fluid contact with blood in the left atrium. In anotherembodiment, the anchor is designed such that the pressure sensor extendsa predetermined distance into the left atrium. In both theseembodiments, the pressure sensor package is located in the septum withits proximal end extending back into the right atrium. A flexible leadextends from the proximal end of the sensor package back through theright atrium, into the superior vena cava, up to a subclavian vein, andout through the wall of the subclavian vein, terminating at an antennacoil assembly located in a subcutaneous pocket near the patient'sclavicle, similar to a pacemaker generator housing.

The temperature at the site of the sensor and an internalelectrocardiogram (IEGM) are also detected by the sensor. A digitalsignal is communicated to an external telemetry device via an antennacoil implanted under the patient's skin and connected to the sensor by aflexible lead. The sensor is powered by radio frequency energy receivedby the implanted coil from an external coil connected to the externaltelemetry device. The external telemetry device forms part of anexternal patient advisory module, that also includes a battery powersource, a signal processor, and a patient signaling device that consistsof a personal data assistant (PDA) with a display screen and softwarefor communicating with the patient.

The external patient advisory module is programmed to alert the patientat times determined by the physician, preferably at the times thepatient is scheduled to take prescribed medications, typically one tothree times per day. In one embodiment, the alert consists of an audiblealarm and the appearance of a written message on the graphical interfaceof the patient-signaling device. The message instructs the patient toperform a “heart check,” that is to obtain physiological measurementsfrom the implanted device. Instructions to the patient may includeinstructions to establish certain standard conditions, such as sittingquietly in a chair, prior to beginning the measurements. The patient isinstructed to place the external telemetry/power coil over the implantedantenna coil, then to press a button to initiate the measurementsequence. Once the patient presses the button, the external devicebegins emits energy via the external coil to power and communicate withthe implanted device. In one embodiment the external device emits anaudible signal while communication is being established, then emits asecond audible signal distinct from the first when communication hasbeen established and while the measurement is taking place. Once themeasurement is concluded, typically after 5 to 20 seconds, a thirdaudible signal, distinct from the first two, is emitted to signal thepatient that the measurement is complete.

In one embodiment, the external device will further instruct thepatient, using its graphical interface, to enter additional informationrelevant to the patient's condition, such as weight, peripheral bloodpressure, and symptoms. The signal processing apparatus of the externaldevice then compares the measured physiological parameters from theimplanted device, together with information entered by the patient, withranges and limits corresponding to different therapeutic actions aspredetermined by the physician and stored in the external device as adynamic prescription or DynamicRx™ (Savacor, Inc.). The prescribedtherapeutic action will then be communicated to the patient on thegraphic display.

In one embodiment, the patient signaling apparatus will prompt thepatient to confirm that each prescribed therapy has been performed. Forexample, if the therapy is taking a specific dose of oral medication,the patient will be prompted to press a button on the graphicalinterface when the medication has been taken. In one embodiment of theinvention, this information is used to keep track of the number of pillsremaining since the last time the patient's prescription was filled, sothat the patient or caregiver can be reminded when it is time to refillthe prescription.

As an example of a DynamicRx™ for a congestive heart failure patient,the level and rate of change of left atrial blood pressure (LAP) may beused by the physician to determine the dosage of diuretic. If the LAPremains in the normal range for that patient, the patient signalingdevice would display the normal dosage of diuretic. As in Example 1above, if the LAP falls below the patient's normal range, the doctor mayprescribe a reduction or withholding of diuretic, and that instructionwould appear on the graphical interface. In another embodiment ofDynamicRx™ the patient may be instructed to take some other kind ofaction, such as calling the physician or caregiver, altering diet orfluid intake, or getting additional rest. Thus, the apparatus andmethods of the present invention allow the physician to conditionallyprescribe therapy for the patient, and to communicate the appropriatetherapy to the patient in response to dynamic changes in the patient'smedical condition.

In one embodiment, the physician enters the therapeutic plan for thepatient, e.g., the DynamicRx™, on a personal computer and the DynamicRx™is then loaded from the PC into the patient advisory module. In oneembodiment, the patient advisory module is a PDA using the PALM OS®(Palm Computing, Inc.), or like operating system, and the DynamicRx™ isloaded from the physician's PC via the HOTSYNC® (Palm Computing, Inc.),or like facility of PALM OS®. Loading of the DynamicRx™ from thephysician's PC could be performed in the physician's office, or could beperformed over a telephone modem or via a computer network, such as theInternet.

In one embodiment, DynamicRx™ software running on the PC containstreatment templates that assist the physician in creating a completeDynamicRx™, such that appropriate therapies/actions are provided for allpossible values of the patient's physiological parameters.

In one embodiment of the present invention, the DynamicRx™ includes apatient instruction. In one embodiment, the patient instruction mayincludes directions or instructions to take medications, instructions tocall 911, instructions to rest; or instructions to call a physician ormedical care provider. In another embodiment of the present invention,one or more devices are provided to enable a physician or medical careprovider to provide instruction to the patient. These devices include,but are not limited to, workstations, templates, PC-to-Palm hotsyncoperations, uploading processes, downloading processes, linking devices,wireless connections, networking, data cards, memory cards, andinterface devices that permit the physician instruction to be loadedonto a patient's signal processor. In another embodiment, a userinstruction is provided, where the user includes a patient, a physician,or a third party.

C. Example 3

Heart failure patients implanted with the embodiments described in theabove two examples may at the time of such implantation, or subsequentlydevelop a medical indication for concurrent implantation of a CRMdevice. For example, required heart failure treatment with beta-blockingmedication may slow the heart rate sufficiently to induce symptoms suchas fatigue, or may prevent the heart rate from increasing appropriatelywith exertion, a condition known as chronotropic incompetence. Theseconditions are recognized indications for atrial pacing or atrial pacingwith a rate responsive type of pacemaker. Normally this involves theplacement of a pacemaker generator and an atrial pacing lead usuallypositioned in the right atrial appendage. In many cases, a dual chamberpacemaker is placed to synchronously pace the right atrium via one leadand the right ventricle via a second pacing lead. In other cases, suchheart failure patients may have an abnormality of electrical conductionwithin the heart such as is known to occur with a condition calledleft-bundle branch block that causes dysynchronous left ventricularcontraction thereby worsening heart failure. Implantation of abiventricular pacemaker has been shown to improve many of thesepatients. Because severe heart failure also carries an increased risk ofsudden cardiac death due to a ventricular cardiac tachyarrhythmia, manyof these patients are now being treated with implantable cardiacdefibrillators (ICD's). In some cases combination rhythm managementdevices comprised of a biventricular pacemaker and an ICD are implanted.

In such cases where a CRM device is needed, it would be beneficial tothe patient if the rhythm management device were integrated with theheart failure management devices described by Eigler, et al., in U.S.Pat. No. 6,328,699 and U.S. Patent Application Publication Nos.2003/0055344 and 2003/0055345, all of which are incorporated byreference in their entireties, to utilize the sensing lead yielding apressure indicative of left atrial pressure additionally as an atrialpacing lead. It would be further beneficial if the LAP sensing leadsystem described in Example 2 could be upgraded to integrated with theheart failure management device without removing or changing the LAPsensing lead.

In one embodiment, the implanted heart failure device of Example 2 aboveis modified by replacing the implanted communications coil with anappropriately integrated CRM generator and additional pacing/ICD leads.The LAP sensing lead is connected as the atrial pacing lead to thegenerator. The generator has appropriate circuitry to power the sensingcircuitry of the atrial lead. LAP is read out by telemetry between theexternal PDA and the telemetry coil in the housing of the integratedrhythm management generator. If clinically appropriate, right and leftventricular pacing or defibrillation leads can be placed and connectedto the generator. There are many potential benefits from such a combinedrhythm and heart failure management system in addition to the clinicalbenefits from each individual system. Fewer leads need to be placed inthe heart and a single venous insertion site can be used with thecombined system. Atrial pacing from the intra-atrial septum has beenshow to inhibit paroxysmal atrial fibrillation, an arrhythmia common inheart failure patients. Patients can be titrated to higher or moreappropriate beta-blocker dose levels with potentially increased survivalbenefits. Additionally, the LAP sensor can be used to control pacingparameters. As described above, the LAP waveform may be helpful inadjusting mechanical left-sided AV delay to optimize LV filling. Also,when LAP is within the desired normal range and thus the patient is notin acute heart failure, synchronous ventricular pacing can be inhibitedto prolong battery life. It is understood by those skilled in the art,such as cardiologists and cardiac surgeons, that there may be additionalclinical benefits bestowed by the combination of heart failure andrhythm management devices.

While this invention has been particularly shown and described withreferences to embodiments thereof, it will be understood by thoseskilled in the art that various changes in form and details may be madetherein without departing from the scope of the invention. For all ofthe embodiments described above, the steps of the methods need not beperformed sequentially.

1. A method of detecting a cardiac condition of a medical patient,comprising: providing a lead to a patient's heart, the lead comprisingfirst and second pressure sensors; positioning the lead such that thefirst pressure sensor is in communication with a left atrium of thepatient's heart and such that the second pressure sensor is incommunication with a right atrium of the patient's heart; sensing afirst pressure in the left atrium of the patient's heart with the firstpressure sensor; sensing a second pressure in the right atrium of thepatient's heart with the second pressure sensor; and monitoring acardiac condition of the patient based upon the first and second sensedpressures.
 2. The method of claim 1, wherein said providing a leadcomprises advancing the lead from the right atrium, through the atrialseptal wall, and into the left atrium of the medical patient.
 3. Themethod of claim 1, wherein said monitoring a cardiac condition comprisesdistinguishing between different causes of congestive heart failure. 4.The method of claim 1, further comprising generating first and secondsignals based upon said sensing first and second pressures,respectively, and storing data related to said first and second signalsin a memory.
 5. The method of claim 1, further comprising communicatingan indication of the cardiac condition to the patient.
 6. A method ofdetecting a cardiac condition of a medical patient, comprising: sensinga first pressure in a left atrium of the patient's heart; sensing asecond pressure in a right atrium of the patient's heart; determining apressure differential between the first pressure and the secondpressure; and monitoring a cardiac condition of the patient based uponthe pressure differential.
 7. The method of claim 6, further comprisingcommunicating said differential pressure to a processor.
 8. The methodof claim 6, wherein said cardiac condition comprises congestive heartfailure.
 9. The method of claim 6, further comprising: providing apressure sensor comprising a first and second pressure sensingmembranes; positioning the first pressure sensing membrane incommunication with the left atrium; and positioning the second pressuresensing membrane in communication with the right atrium.
 10. The methodof claim 6, further comprising communicating an indication of thecardiac condition to the patient.
 11. A system for monitoring a cardiaccondition of a medical patient, comprising: a first pressure sensor,configured to provide a first signal indicative of fluid pressure withina left atrium of the patient's heart; a second pressure sensor,configured to provide a second signal indicative of fluid pressurewithin a right atrium of the patient's heart; and a processor,configured to receive the first and second signals and to determine apressure differential between the first and second signals, wherein thepressure differential is indicative of the pressure difference betweenthe fluid pressures within the left and right atria of the patient'sheart, and wherein the processor is further configured to determine acardiac condition of the patient based upon the pressure differential.12. The system of claim 11, wherein the cardiac condition comprisescongestive heart failure.
 13. The system of claim 11, further comprisinga lead in communication with said first and second pressure sensors, andsaid processor.
 14. The system of claim 13, wherein said first pressuresensor is positioned at a distal end of said lead.
 15. The system ofclaim 13, wherein said second pressure sensor is between said firstpressure sensor and said processor.
 16. The system of claim 13, whereinsaid second pressure sensor is positioned on an exterior of said lead.17. The system of claim 11, further comprising one or more additionalsensors configured to provide one or more additional sensor signals tosaid processor.
 18. The system of claim 11, further comprising acommunications module configured to communicate the first and secondsignals to said processor.
 19. The system of claim 11, furthercomprising a power storage device.